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Sample records for acid-induced status epilepticus

  1. Administration of Simvastatin after Kainic Acid-Induced Status Epilepticus Restrains Chronic Temporal Lobe Epilepsy

    Xie, Chuncheng; Sun, Jiahang; Qiao, Weidong; Lu, Dunyue; Wei, Lanlan; NA, MENG; Song, Yuanyuan; Hou, Xiaohua; LIN, ZHIGUO

    2011-01-01

    In this study, we examined the effect of chronic administration of simvastatin immediately after status epilepticus (SE) on rat brain with temporal lobe epilepsy (TLE). First, we evaluated cytokines expression at 3 days post KA-lesion in hippocampus and found that simvastatin-treatment suppressed lesion-induced expression of interleukin (IL)-1β and tumor necrosis factor-α (TNF-α). Further, we quantified reactive astrocytosis using glial fibrillary acidic protein (GFAP) staining and neuron los...

  2. Status Epilepticus.

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

    2016-01-01

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

  3. Fresh green tea and gallic acid ameliorate oxidative stress in kainic acid-induced status epilepticus.

    Huang, Hsiao-Ling; Lin, Chih-Cheng; Jeng, Kee-Ching G; Yao, Pei-Wun; Chuang, Lu-Te; Kuo, Su-Ling; Hou, Chien-Wei

    2012-03-01

    Green tea is one of the most-consumed beverages due to its taste and antioxidative polyphenols. However, the protective effects of green tea and its constituent, gallic acid (GA), against kainic acid (KA)-induced seizure have not been studied. We investigated the effect of fresh green tea leaf (GTL) and GA on KA-induced neuronal injury in vivo and in vitro. The results showed that GTL and GA reduced the maximal seizure classes, predominant behavioral seizure patterns, and lipid peroxidation in male FVB mice with status epilepticus (SE). GTL extract and GA provided effective protection against KA-stressed PC12 cells in a dose-dependent manner. In the protective mechanism study, GTL and GA decreased Ca(2+) release, ROS, and lipid peroxidation from KA-stressed PC12 cells. Western blot results revealed that mitogen-activated protein kinases (MAPKs), RhoA, and COX-2 expression were increased in PC12 cells under KA stress, and expression of COX-2 and p38 MAPK, but not RhoA, was significantly reduced by GTL and GA. Furthermore, GTL and GA were able to reduce PGE(2) production from KA-stressed PC12 cells. Taken together, the results showed that GTL and GA provided neuroprotective effects against excitotoxins and may have a clinical application in epilepsy. PMID:22324774

  4. Partial motor status epilepticus

    Gilberto Rebello de Mattos; José C. Rollemberg Filho

    1992-01-01

    We report the case of a young female patient with photosensitive primary epilepsy who presented partial motor status epilepticus provoked by the act of shutting the eyes. Clinical, EEG and neuroimage data are presented and discussed.

  5. STATUS EPILEPTICUS: A REVIEW

    B. Adibeik

    2009-01-01

    Full Text Available ObjectiveStatus Epilepticus (SE has been described as a series of major motor seizure without recovery of consciousness between seizures.SE is a medical emergency that requires prompt diagnosis and appropriate treatment.In this article we shall conclude history, epidemiology, etiology, risk factors, thebest management as well as the prognosis of the condition.Keywords:Status Epilepticus (SE, adults, children, neonates.

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

    Hanna B Laurén

    Full Text Available 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

  7. Refractory status epilepticus

    Sanjay P Singh

    2014-01-01

    Full Text Available Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED, i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits.

  8. Pharmacotherapy for Status Epilepticus

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

    2015-01-01

    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...

  9. STATUS EPILEPTICUS: A REVIEW

    B. Adibeik

    2008-10-01

    Full Text Available ObjectiveStatus Epilepticus (SE has been described as a series of major motor seizure without recovery of consciousness between seizures.SE is a medical emergency that requires prompt diagnosis and appropriate treatment.In this article we shall conclude history, epidemiology, etiology, risk factors, thebest management as well as the prognosis of the condition.

  10. Nonconvulsive Status Epilepticus

    Ayhan Aköz

    2014-08-01

    Full Text Available Status epilepticus (SE can be divided into two subgroups, convulsive status epilepticus (CSE and nonconvulsive status epilepticus (NCSE. NCSE is clinically characterized by recurrence or persistence of absence or complex partial seizures which unconsciousness persists. Seizures are lasted more than 30 minutes, and accompanied by mental and behavioral changes. Although the main feature is the change of level of consciousness, affective, memory, cognitive, speech, motor systems, behavioral and psychiatric disorders can be also seen. Electroencephalography (EEG is the single diagnostic method in this situation. NCSE constitutes approximately 25% of all SE, however it is thought that sometimes it is misdiagnosed and the incidence of NCSE may be higher. The causes are disorders of central nervous system (stroke, infection, trauma, tumor, and metabolic factors (hypoxia, renal diseases, drugs, failure to use antiepileptic drug. The treatment contains the standard therapy of SE. Short-acting benzodiazepines are preferred in initial treatment. For more resistant cases, loading of phenytoin is applied. If there is no response to treatment, midazolam and propofol additionally to barbiturates can be used. We aimed to present a case admitted to our ED with altered mental status and diagnosed as NCSE that is under-diagnosed.

  11. Status epilepticus in scleromyxedema

    Soifa Markoula; Soifa Zouroudi; Soitrios Giannopoulos; Kimon Tsoukanelis; Ananstasia Zikou; Athanassios P Kyritsis

    2016-01-01

    Scleromyxedema is a rare dermatologic disorder, characterized by erythematous or yelowish lichenoid waxy papules. Neurological manifestations are rare but wel-recognized. A 51-year-old woman, diagnosed with scleromyxedema, was admitted to the hospital with status epilepticus, caused by brain lesions, as disclosed in a brain magnetic resonance imaging (MRI). The patient was treated with anticonvulsants and corticosteroids and gradualy recovered fuly. A complete remission of the lesions was shown in a folow-up brain MRI. In cases with scleromyxedema and the presence of neurological manifestations, we need to pay attention to central nervous system involvement, especialy when combined with brain MRI lesions, and treat the patient appropriately.

  12. Pharmacotherapy for Status Epilepticus.

    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

  13. Sesamin ameliorates oxidative stress and mortality in kainic acid-induced status epilepticus by inhibition of MAPK and COX-2 activation

    Lin Ching-Huei; Shen Mei-Lin; Peng Yu-Fen; Wu Szu-Pei; Yao Pei-Wun; Hou Chien-Wei; Hsieh Peiyuan F; Chao Ya-Yun; Chang Ming-Hong; Jeng Kee-Ching

    2011-01-01

    Abstract Background Kainic acid (KA)-induced status epilepticus (SE) was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied. Methods Rodents (male FVB mice and Sprague-Dawley rats) were fed with sesamin extract (90% of sesamin and 10% sesamolin), 15 mg/kg or 30 mg/kg, for 3 days before KA subcutane...

  14. Outcome of Refractory Status Epilepticus

    J Gordon Millichap

    2002-01-01

    Full Text Available The records of twenty-two children, ages 4.5 months to 18 years, treated for refractory status epilepticus (RSE between 1992 and 2000, were reviewed retrospectively at Children’s Hospital, Boston.

  15. Management of Status Epilepticus in Children

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

    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.

  16. Sesamin ameliorates oxidative stress and mortality in kainic acid-induced status epilepticus by inhibition of MAPK and COX-2 activation

    Lin Ching-Huei

    2011-05-01

    Full Text Available Abstract Background Kainic acid (KA-induced status epilepticus (SE was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied. Methods Rodents (male FVB mice and Sprague-Dawley rats were fed with sesamin extract (90% of sesamin and 10% sesamolin, 15 mg/kg or 30 mg/kg, for 3 days before KA subcutaneous injection. The effect of sesamin on KA-induced cell injury was also investigated on several cellular pathways including neuronal plasticity (RhoA, neurodegeneration (Caspase-3, and inflammation (COX-2 in PC12 cells and microglial BV-2 cells. Results Treatment with sesamin extract (30 mg/kg significantly increased plasma α-tocopherol level 50% and 55.8% from rats without and with KA treatment, respectively. It also decreased malondialdehyde (MDA from 145% to 117% (p = 0.017 and preserved superoxide dismutase from 55% of the vehicle control mice to 81% of sesamin-treated mice, respectively to the normal levels (p = 0.013. The treatment significantly decreased the mortality from 22% to 0% in rats. Sesamin was effective to protect PC12 cells and BV-2 cells from KA-injury in a dose-dependent manner. It decreased the release of Ca2+, reactive oxygen species, and MDA from PC12 cells. Western blot analysis revealed that sesamin significantly reduced ERK1/2, p38 mitogen-activated protein kinases, Caspase-3, and COX-2 expression in both cells and RhoA expression in BV-2 cells. Furthermore, Sesamin was able to reduce PGE2 production from both cells under KA-stimulation. Conclusions Taken together, it suggests that sesamin could protect KA-induced brain injury through anti-inflammatory and partially antioxidative mechanisms.

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

    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

  18. Genetic mutations associated with status epilepticus.

    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

  19. [Simple partial frontal nonconvulsive status epilepticus].

    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

  20. Nonconvulsive status epilepticus disguising as hepatic encephalopathy

    Jo, Yong Min; Lee, Sung Wook; Han, Sang Young; Baek, Yang Hyun; Ahn, Ji Hye; Choi, Won Jong; Lee, Ji Young; Kim, Sang Ho; Yoon, Byeol A

    2015-01-01

    Nonconvulsive status epilepticus has become an important issue in modern neurology and epileptology. This is based on difficulty in definitively elucidating the condition and its various clinical phenomena and on our inadequate insight into the intrinsic pathophysiological processes. Despite nonconvulsive status epilepticus being a situation that requires immediate treatment, this disorder may not be appreciated as the cause of mental status impairment. Although the pathophysiology of nonconv...

  1. Prognostic Factors for Refractory Status Epilepticus

    J. Gordon Millichap

    2013-03-01

    Full Text Available Researchers at the Mayo Clinic, Rochester, MN studied the outcome and identified prognostic factors for refractory status epilepticus (RSE in 54 adult patients, median age 52 years [range 18-93].

  2. Managing Status Epilepticus in the Older Adult

    Stephane Legriel; 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 associat...

  3. Nonconvulsive status epilepticus after electroconvulsive therapy

    Povlsen, Uffe Juul; Wildschiødtz, Gordon; Høgenhaven, Hans;

    2003-01-01

    SUMMARY: We describe three cases of nonconvulsive status epilepticus induced by electroconvulsive therapy (ECT). Nonconvulsive status epilepticus is an important differential diagnosis in patients who develop prolonged confusion after ECT. The present cases exemplify the difficulty in defining the...... diagnosis on the basis of the clinical manifestations. The application of electroencephalography is recommended in monitoring patients with prolonged confusion following ECT. Concurrent drug therapy and ECT is discussed....

  4. Early Developmental Outcome Following Convulsive Status Epilepticus

    J Gordon Millichap

    2013-08-01

    Full Text Available Investigators at the Developmental Cognitive Neurosciences Unit, Institute of Child Health, London, other centers in the UK, and Dartmouth School of Medicine, NH, USA, prospectively recruited children aged between 1 and 42 months from North London who had at least one episode of convulsive status epilepticus (CSE and classified them as prolonged febrile seizures (PFS or nonfebrile CSE.

  5. Risk of Status Epilepticus in Epilepsy

    J Gordon Millichap

    2004-10-01

    Full Text Available The occurrence of status epilepticus (SE after the initial diagnosis of epilepsy was determined in a prospective community-based cohort study of 613 children at Montefiore Medical Center, Bronx, NY; Yale Medical School, New Haven, CT; and BIOS/NIU, DeKalb, IL.

  6. Acute polyhydramnios after maternal status epilepticus

    Shindo, Ryosuke; Aoki, Shigeru; Kasai, Michi; Takahashi, Tsuneo; Hirahara, Fumiki

    2015-01-01

    Key Clinical Message Maternal status epilepticus can cause fetal hypoxic ischemic encephalopathy that in turn results in acute polyhydramnios caused by fetal dysphagia; thus, acute polyhydramnios is a symptom that should lead to a suspicion of fetal dysphagia caused by hypoxic ischemic encephalopathy.

  7. Management of super refractory status epilepticus with isoflurane and hypothermia

    Charles Patrick Gilman

    2015-01-01

    Full Text Available Super-refractory status epilepticus is status epilepticus that continues beyond 24 hours and includes those cases in which epilepsy is recurrent upon reduction or withdrawal of treatment. We describe the presentation and successful management of a male patient with super-refractory status epilepticus using the inhaled anesthetic, isoflurane, and mild hypothermia (HT. The potential utility of combined HT and volatile anesthesia is discussed.

  8. Management of super refractory status epilepticus with isoflurane and hypothermia

    Charles Patrick Gilman

    2015-01-01

    Super-refractory status epilepticus is status epilepticus that continues beyond 24 hours and includes those cases in which epilepsy is recurrent upon reduction or withdrawal of treatment. We describe the presentation and successful management of a male patient with super-refractory status epilepticus using the inhaled anesthetic, isoflurane, and mild hypothermia (HT). The potential utility of combined HT and volatile anesthesia is discussed.

  9. Status epilepticus: Analysis of refractory cases

    B. P. Gladov; O. A. Podgornaya; P. N. Vlasov

    2016-01-01

    Objective: to analyze refractory status epilepticus (SE) cases.Patients and methods. Fifteen female patients aged 21 to 62 years with refractory SE were comprehensively examined using long-term electroencephalography monitoring. The investigators evaluated the efficiency of treatment regimens with intravenous antiepileptic drugs (AEDs), such as diazepam (DZP); valproic acid (VPA); levetiracetam; and lacosamide and their combinations, at the prehospital and hospital stages, as well as SE thera...

  10. Managing Status Epilepticus in the Older Adult.

    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

  11. Managing Status Epilepticus in the Older Adult

    Stephane Legriel

    2016-05-01

    Full Text Available 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.

  12. Pediatric Super-Refractory Status Epilepticus Treated with Allopregnanolone

    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

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

    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

  14. New lessons: Classic treatments in convulsive status epilepticus.

    Renganathan, R

    2012-02-03

    Convulsive status epilepticus is a relatively common life-threatening illness requiring prompt intervention. There has been much debate about the appropriate protocol for management of convulsive status epilepticus. Published data on the management of this condition in Ireland is limited. Our aim was to establish if there was a structured, evidence-based or consensus-based protocol being implemented in the management of status epilepticus in our centre. We retrospectively audited all charts with a diagnosis of \\'Status Epilepticus\\' admitted to our hospital from January 1998 to December 2002. A total of 95 episodes of convulsive status epilepticus were recorded. 34 charts were reviewed. Benzodiazepines were the drug class of first choice in 96% of patients. However, the doses of benzodiazepines used varied widely. The most frequent dose of phenytoin used was 1 gram. No one received continuous EEG monitoring during treatment of refractory status epilepticus. Overall mortality was 18%. The results of this study show that there is no consistent protocol was being followed for the management of convulsive status epilepticus in our centre. The drugs of first choice varied between diazepam and lorazepam in most cases. Although phenytoin was used as second line drug, the dose used was frequently suboptimal. We have developed a protocol for the management for convulsive status in our centre.

  15. Prallethrin Poisoning Presenting as Status Epilepticus

    D Vijayaraju

    2014-02-01

    Full Text Available Mosquito repellents contain pyrethroid derivatives, as the active ingredient. Data regarding human toxicity following oral intake is limited. This is a case report of an individual who presented with neurotoxicity following oral ingestion of prallethrin (2.4% w/w of a higher concentration present in formulations commercially available than previously. A 22 year old male presented to the emergency Room (ER in status epilepticus. He was managed in the Intensive Care Unit (ICU. No cause for his status could be determined after all laboratory investigations. A review of history with the patient revealed that he had ingested a bottle of liquid mosquito repellent (45 ml. The patient has had no further symptoms on follow up and has been off anti epileptics. Pyrethroid containing mosquito repellents act on neuronal sodium channels causing hyperexcitiability. With no known specific antidotes, symptomatic treatment is the main stay of management.

  16. Clinical decision making in seizures and status epilepticus.

    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. Emergency Neurological Life Support: Status Epilepticus.

    Claassen, Jan; Riviello, James J; Silbergleit, Robert

    2015-12-01

    Patients with prolonged or rapidly recurring convulsions lasting more than 5 min are in status epilepticus (SE) and require immediate resuscitation. Although there are relatively few randomized clinical trials, available evidence and experience suggest that early and aggressive treatment of SE improves patient outcomes, for which reason this was chosen as an Emergency Neurological Life Support protocol. The current approach to the emergency treatment of SE emphasizes rapid initiation of adequate doses of first-line therapy, as well as accelerated second-line anticonvulsant drugs and induced coma when these fail, coupled with admission to a unit capable of neurological critical care and electroencephalography monitoring. This protocol will focus on the initial treatment of SE but also review subsequent steps in the protocol once the patient is hospitalized. PMID:26438462

  18. Primary Amoebic (Naegleria fowleri Meningoencephalitis Presenting as Status Epilepticus

    A Sharma

    2011-04-01

    Full Text Available Primary amebic meningoencephalitis (PAM is a rare entity. Usual presenting features are fever, headache and seizures with meningeal signs and this disease carries high mortality rate. We present a case report of PAM presenting as status epilepticus.

  19. Ketogenic diet in 3 cases of childhood refractory status epilepticus

    Sort, Rune; Born, Alfred P; Pedersen, Karen N.;

    2013-01-01

    Refractory status epilepticus (RSE) in children is associated with a significant risk of death or neurological morbidity. Recently attention has been drawn to the ketogenic diet (KD) as an acute treatment, as it has shown promise in controlling seizures in otherwise refractory status epilepticus in...... several cases. We have listed these and reviewed all cases of KD used in RSE at our centre. KD was given as 4:1 fat:carbohydrate-protein solution....

  20. Status epilepticus: Analysis of refractory cases

    B. P. Gladov

    2016-01-01

    Full Text Available Objective: to analyze refractory status epilepticus (SE cases.Patients and methods. Fifteen female patients aged 21 to 62 years with refractory SE were comprehensively examined using long-term electroencephalography monitoring. The investigators evaluated the efficiency of treatment regimens with intravenous antiepileptic drugs (AEDs, such as diazepam (DZP; valproic acid (VPA; levetiracetam; and lacosamide and their combinations, at the prehospital and hospital stages, as well as SE therapy complications noted only in the intravenous administration of narcotics (propofol, sodium thiopental.Results and discussion. A fetal outcome due to multiple organ dysfunction indirectly related to SE was recorded in 2 (13.3% patients with acute symptomatic status. SE was abolished in the other 13 cases. The preliminary findings may suggest that it is appropriate to prescribe VPA just at the prehospital stage. The co-administration of VPA and DZP substantially enhances the efficiency of SE therapy. The maximum acceptable doses of AEDs using the whole available therapeutic arsenal should be administered within the first hours of acute symptomatic SE.

  1. Cocaine-Associated Seizures and Incidence of Status Epilepticus

    Majlesi, Nima DO

    2010-05-01

    Full Text Available Objectives: Acute complications from cocaine abuse are commonly treated in the emergency department (ED; one of the most consequential is status epilepticus. The incidence of this complication is not clearly defined in the prior literature on cocaine-associated sequelae. We evaluated the incidence of status epilepticus in patients with seizures secondary to suspected cocaine use.Methods: We performed a retrospective multi-center study of patients with seizures resulting from cocaine use. We identified study subjects at 15 hospitals by record review and conducted a computer-assisted records search to identify patients with seizures for each institution over a four-year period. We selected subjects from this group on the basis of cocaine use and determined the occurrence of status epilepticus among them. Data were collected on each subject using a standardized data collection form.Results: We evaluated 43 patients in the ED for cocaine-associated seizures. Their age range was 17 to 54, with a mean age was 31 years; 53% were male. Of 43 patients, 42 experienced a single tonic-clonic seizure and one developed status epilepticus. All patients had either a history of cocaine use or positive urine drug screen for cocaine.Conclusion: Despite reported cases of status epilepticus with cocaine-induced seizures, the incidence of this complication was unclear based on prior literature. This study shows that most cocaine-associated seizures are self-limited. [West J Emerg Med. 2010; 11(2:157-160.

  2. Status epilepticus in the elderly: differential diagnosis and treatment

    Mauricio EA

    2011-03-01

    Full Text Available Elizabeth Ann Mauricio, William David FreemanMayo Clinic, Jacksonville, FL, USADate of Preparation 28th January 2011 Conflict of interest: None declaredAbstract: Seizures are not an uncommon occurrence in older adults, and the incidence of status epilepticus is much greater in the elderly than in younger populations. Status epilepticus is a neurologic emergency and requires prompt intervention to minimize morbidity and mortality. Treatment involves both supportive care as well as initiation of medications to stop all clinical and electrographic seizure activity. Benzodiazepines are used as first-line agents, followed by antiepileptic drugs when seizures persist. In refractory status epilepticus, urgent neurologic consultation is indicated for the titration of anesthetic agents to a level of appropriate background suppression on EEG. In light of our aging population, physician awareness and competence in the management of status epilepticus is imperative and should be recognized as a growing public health concern.Keywords: status epilepticus, convulsive, generalized, nonconvulsive, refractory, elderly, treatment 

  3. How to Manage Electrical Status Epilepticus in Sleep.

    Veggiotti, Pierangelo; Pera, Maria Carmela; Olivotto, Sara; De Giorgis, Valentina

    2016-02-01

    Electrical status epilepticus in sleep is an age-dependent syndrome with the characteristic pattern of continuous spike and waves during non-rapid eye movement sleep. Most children can present developmental deterioration. The demonstration of the EEG pattern has to rely on all night long EEG recordings. A comprehensive neuropsychologic evaluation with periodic reassessment should be performed. For the idiopathic forms of electrical status epilepticus in sleep, clobazam could be considered as the first-line therapy; in the other cases, corticosteroids, in particular intravenous methylprednisolone pulse therapy, remain the most effective and should be considered the therapy of choice. PMID:26840869

  4. On Etiology and Mortality Rate of Status Epilepticus

    F Ashraf Zadeh

    2000-01-01

    The etiology and mortality rate of Status Epilepticus in 60 pediatric patients, aged 2 months to 13 years, during 10 years has been evaluated. The results show that: -41.7% of the patients were female and 58.3% male. -65% of patients were<3 years and 35% >3 years old. - Mortality rate was 21.6%, 46.1% of which were referral patients. -Major causes of Status Epilepticus were: Idiopathic epilepsy 33%, prolonged febrile seizure 17%, electrolyte imbalance 13%, meningitis 10%, sepsis 8%, enc...

  5. Consequences of Inappropriate ER Management of Status Epilepticus

    J Gordon Millichap

    2004-11-01

    Full Text Available The clinical features of status epilepticus (SE requiring admission to pediatric intensive care (PTC and the emergency pre-PIC treatment of SE compared to standard guidelines were studied in relation to the course of SE after admission to PIC at Great Ormond Street Hospital for Children, London, UK.

  6. Partial status epilepticus - rapid genetic diagnosis of Alpers' disease.

    McCoy, Bláthnaid

    2011-11-01

    We describe four children with a devastating encephalopathy characterised by refractory focal seizures and variable liver dysfunction. We describe their electroencephalographic, radiologic, genetic and pathologic findings. The correct diagnosis was established by rapid gene sequencing. POLG1 based Alpers\\' disease should be considered in any child presenting with partial status epilepticus.

  7. On Etiology and Mortality Rate of Status Epilepticus

    F Ashraf Zadeh

    2000-07-01

    Full Text Available The etiology and mortality rate of Status Epilepticus in 60 pediatric patients, aged 2 months to 13 years, during 10 years has been evaluated. The results show that: -41.7% of the patients were female and 58.3% male. -65% of patients were<3 years and 35% >3 years old. - Mortality rate was 21.6%, 46.1% of which were referral patients. -Major causes of Status Epilepticus were: Idiopathic epilepsy 33%, prolonged febrile seizure 17%, electrolyte imbalance 13%, meningitis 10%, sepsis 8%, encephalitis 5%, encephalopathy 5%, cerebral palsy 5%, intracranial hemorrhage 1.6%, inborn error of metabolism 1.6%. -No mortality occurred in patients with febrile seizures and electrolyte imbalance.

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

    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. Nonconvulsive status epilepticus secondary to paclitaxel administration ☆

    Ignacio Illán-Gala; Francisco Javier Díaz de Terán; Pablo Alonso; María-José Aguilar-Amat

    2015-01-01

    Nonconvulsive status epilepticus (NCSE) can be triggered by metabolic disturbances and drugs in adults without previous epilepsy. We present the case of a 51-year-old woman without previous history of epilepsy and recently diagnosed with infiltrating lobular breast carcinoma. Following the administration of paclitaxel–cremophor, she presented a striking disinhibited behavior with episodic spatial disorientation, emotional indifference, and irritability. Urgent EEG was consistent with NCSE. Cl...

  10. Complex partial status epilepticus associated with cyclosporin A therapy.

    Appleton, R E; Farrell, K; Teal, P.; Hashimoto, S.A.; Wong, P K

    1989-01-01

    Significant neurotoxicity including seizures, encephalopathy and coma may complicate the use of cyclosporin A (CyA). Two patients are described, receiving CyA, who presented with abnormal behaviour, stupor, focal motor activity and were shown to be in complex partial status epilepticus (CPSE). Abnormalities of behaviour and/or stupor in patients receiving CyA may be a manifestation of CPSE. Patients receiving CyA who develop an encephalopathy should have electroencephalography performed at th...

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

    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 req...

  12. Pediatric Super-Refractory Status Epilepticus Treated with Allopregnanolone

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

    2014-01-01

    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 allopregnano...

  13. STATUS EPILEPTICUS: ETIOLOGY, OUTCOME AND PREDICTORS OF MORTALITY

    A. Moayedi; A. Atashabparvar; E.Eftekhari

    2008-01-01

    ObjectiveThis study was designed to determine the etiology of status epilepticus (SE) andits relation to mortality.Materials and MethodsThis descriptive study was carried out based on the medical records of 40 patients with diagnosis of SE discharged from pediatric hospital of Bandar Abbas between March 2002 and March 2004. Multivariant analysis was pereformed to determine the prevalence of the disorder and the relation between SE and other factors such as gender, age, response to treatment, ...

  14. Cefepime- Induced Non-Convulsive Status Epilepticus (NCSE)

    Kim, Ahro; KIM, Ji-Eun; Paek, Young-Min; Hong, Keun-Sik; Cho, Young-Jin; Cho, Joong-Yang; Park, Hee-Kyung; Koo, Hyeon-Kyoung; Song, Pamela

    2013-01-01

    Cefepime is a fourth-generation B-lactam cephalosporin, commonly used in immunosuppressed patients. Neurotoxicity, which present as nonconvulsive status epilepticus (NCSE), has been reported previously especially in adult patients with impaired renal function. We present a case of cefepime induced NCSE after recovering from acute renal failure. A 71-year-old woman was hospitalized for right lower lobe lobectomy after diagnosis of lung cancer. Although she had successful lobectomy, she underwe...

  15. STATUS EPILEPTICUS: ETIOLOGY, OUTCOME AND PREDICTORS OF MORTALITY

    A. Moayedi

    2008-11-01

    Full Text Available ObjectiveThis study was designed to determine the etiology of status epilepticus (SE andits relation to mortality.Materials and MethodsThis descriptive study was carried out based on the medical records of 40 patients with diagnosis of SE discharged from pediatric hospital of Bandar Abbas between March 2002 and March 2004. Multivariant analysis was pereformed to determine the prevalence of the disorder and the relation between SE and other factors such as gender, age, response to treatment, and mortality. We classified the etiology according to international league against epilepsy (ILAE classification and also uses another classification regarding underlying causes such as fever (non-CNS infection, central nervous system infection, hypoxia, and metabolic causes.ResultsStatus epilepticus was responsible for 0.3% of all hospital  dmissions during the study period. Based on the ILAE classification, frequencies for acute symptomatic, febrile, progressive encephalopathic, remote, and cryptogenic SE were 42.5%, 32.5%, 10%, 7.5%, and 7.5%, respectively.The most common underlying causes resulting in SE were fever (45%, metabolic disorders (15%, CNS infection (12.5%, chronic neurologic diseases (7.5%, idiopathic (7.5%, hypoxia (5%, drug withdrawal (2.5%, CNS hemorrhage (2.5%, neurodegenerative disease (2.5%, brain abscess (2.5%, and post DPT (Diphteria,Pertusis,Tetanus vaccination (2.5%. Mortality rate was 25% (80% in the patients younger than 5 years and 40% in those aged less than 1 year. Occurrence of SE and its mortality was found to be related to age (pConclusionFor SE, if seizures continue for more than 5 minutes, treatment must beinitiated. The outcome is determined by etiology, age, seizure duration and management; however, all we can do is enhance the management and increase its effectiveness.Keywords:Status epilepticus, Etiology, Underlying cause

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

    Fjølner, Jesper; Opstrup, Ulla Kampmann; Søndergaard, Esben;

    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...

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

    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

  18. Generalized status epilepticus associated with massive pulmonary aspiration and transient central diabetes insipidus: case report

    CARVALHO MAURICIO

    2000-01-01

    Full Text Available Status epilepticus causes significant morbidity and mortality. A case of generalized status epilepticus followed by massive pulmonary aspiration, acute respiratory failure and transient central diabetes insipidus is presented. Seizures were promptly controlled, but the patient required mechanical ventilation and correction of polyuria with desmopressin acetate. During hospitalization mental status improved, diabetes insipidus spontaneously remitted and he was discharged without neurologic sequelae. The clinical and pathophysiological features of this case are discussed.

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

    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

  20. STATUS EPILEPTICUS: ETIOLOGY, OUTCOME AND PREDICTORS OF MORTALITY

    A. Moayedi

    2007-11-01

    Full Text Available ObjectiveThis study was designed to determine the etiology of status epilepticus (SE and its relation to mortality.Materials and MethodsThis descriptive study was carried out based on the medical records of 40 patients with diagnosis of SE discharged from pediatric hospital of Bandar Abbas between March 2002 and March 2004. Multivariant analysis was pereformed to determine the prevalence of the disorder and the relation between SE and other factors such as gender, age, response to treatment, and mortality. We classified the etiology according to international league against epilepsy (ILAE classification and also uses another classification regarding underlying causes such as fever (non-CNS infection, central nervous system infection, hypoxia, and metabolic causes.Results Status epilepticus was responsible for 0.3% of all hospital admissions during the study period. Based on the ILAE classification, frequencies for acute symptomatic, febrile, progressive encephalopathic, remote, and cryptogenic SE were 42.5%, 32.5%, 10%, 7.5%, and 7.5%, respectively.The most common underlying causes resulting in SE were fever (45%, metabolic disorders (15%, CNS infection (12.5%, chronic neurologic diseases (7.5%, idiopathic (7.5%, hypoxia (5%, drug withdrawal (2.5%, CNS hemorrhage (2.5%, neurodegenerative disease (2.5%, brain abscess (2.5%, and post DPT(Diphteria,Pertusis,Tetanus vaccination (2.5%. Mortality rate was 25% (80% in the patients younger than 5 years and 40% in those aged less than 1 year. Occurrence of SE and its mortality was found to be related to age (p< 0.05.ConclusionFor SE, if seizures continue for more than 5 minutes, treatment must be initiated. The outcome is determined by etiology, age, seizure duration and management; however, all we can do is enhance the management and increase its effectiveness.

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

    Pavlidis, Elena; Rubboli, Guido; Nikanorova, Marina;

    2015-01-01

    Encephalopathy with status epilepticus during sleep (ESES) is an age-related disorder characterized by neuropsychological regression, epilepsy and a typical EEG pattern of continuous epileptiform activity (> 85%) during NREM sleep. Cases of worsening or induction of ESES with phenytoin...

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

    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

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

    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.

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

    Michael E. Reznik; Karen Berger; Jan Claassen

    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 provid...

  5. STATUS EPILEPTICUS IN CHILDREN CLINICO ETIOLOGICAL PROFILE AND OUTCOME

    Gunasekhara Raju

    2015-11-01

    Full Text Available Status epilepticus is a common condition in acute medical care. Approximately 4.5 million SE events occur worldwide every year.SE in children differs from adult SE in aspects of epidemiology, pathophysiology and clinical presentations, which justifies a separate analysis. The incidence in children is about 18-20/100,000 children/year and distribution of etiologies is markedly age-dependent: Febrile and acute symptomatic convulsive SE is most common in children aged less than 2 years, whereas cryptogenic/idiopathic and remote symptomatic etiologies are more common in older children. A prospective study where 46 children, admitted in Pediatric Intensive Care Unit with seizures lasting >30 minutes in King George Hospital, Visakhapatnam, were studied over a period from 2012 June to 2013 oct. These patients were evaluated for their clinical presentation, laboratory parameters, treatment profile and immediate outcome. As mortality is higher in younger age groups and status with acute symptomatic etiology, there is a need to aggressively treat these groups. As the longer a seizure continues the harder it is to be controlled and as both the mortality and sequelae were found to be significantly lesser in the patients who attained good seizure control within 1 hour of presentation to the hospital.

  6. Is Favorable Outcome Possible After Prolonged Refractory Status Epilepticus?

    Alvarez, Vincent; Drislane, Frank W

    2016-02-01

    When status epilepticus (SE) remains refractory to appropriate therapy, it is associated with high mortality and with substantial morbidity in survivors. Many outcome predictors such as age, seizure type, level of consciousness before treatment, and mostly, etiology, are well-established. A longer duration of SE is often associated with worse outcome, but duration may lose its prognostic value after several hours. Several terms and definitions have been used to describe prolonged, refractory SE, including "malignant SE," "prolonged" SE, and more recently, "super refractory" SE, defined as "SE that has continued or recurred despite 24 hours of general anesthesia (or coma-inducing anticonvulsants)." There are few data available regarding the outcome of prolonged refractory SE, and even fewer for SE remaining refractory to anesthetic drugs. This article reviews reports of outcome after prolonged, refractory, and "super refractory" SE. Most information detailing the clinical outcome of patients surviving these severe illnesses, in which seizures can persist for days or weeks (and especially those concerning "super-refractory" SE) come from case reports and retrospective cohort studies. In many series, prolonged, refractory SE has a mortality of 30% to 50%, and several studies indicate that most survivors have a substantial decline in functional status. Nevertheless, several reports demonstrate that good functional outcome is possible even after several days of SE and coma induction. Treatment of refractory SE should not be withdrawn from younger patients without structural brain damage at presentation solely because of the duration of SE. PMID:26840875

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

    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

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

    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

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

    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

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

    F. A. Zeiler

    2015-01-01

    Full Text Available 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.

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

    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

  12. Levetiracetam versus phenytoin in management of status epilepticus.

    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

  13. MIDAZOLAM EFFICACY AND SIDE EFFECTS IN GENERALIZED AND PARTIAL REFRACTORY STATUS EPILEPTICUS IN CHILDREN

    M.R. Salehi Omran

    2009-04-01

    Full Text Available ObjectiveMidazolam is a significant and effective drug for control of a life-threatening condition, generalized and partial refractory convulsive status epilepticus. The goal of this study was evaluation of midazolam efficacy for management of this serious disease and its two side effects, hypotension and respiratory failure.Materials & MethodsOur study was done using a quasi experimental method; 22 children with generalized refractory convulsive status epilepticus and 13 with partial refractory convulsive status epilepticus were enrolled for the study. All patients received 0.2mg/kg/dose as a bolus intravenous midazolam followed by 1-6 mcg/kg/min continuous intravenous midazolam. Following this, termination of seizures as well as hypotension and respiratory failure were evaluated.ResultsMidazolam ceased stop convulsions in 81.81% (18 patients with generalized seizures, and in 76.92% (10 patients with partial seizures, showing no significant difference between these two types of seizures (p=0.52 Hypotension was induced in 18.18% (4 patients with generalized seizures and in 30.70% (4 patients with partial seizures, again difference not significant (p=0.14. There was respiratory failure in 21.73% (5 patients with generalized seizure and in 7.69% (1 patients with partial seizure, difference not significant.(p=0.09ConclusionThere was no significant difference in efficacy and creation of hypotension and respiratory failure after continuous intravenous infusion of midazolam between generalized and partial refractory convulsive status epilepticus.Key words:Midazolam, Refractory convulsive status epilepticus, Convulsive status epilepticus.

  14. Changes on diffusion-weighted MRI with focal motor status epilepticus: case report

    Transient imaging abnormalities, including changes on diffusion-weighted imaging (DWI), may be seen in focal status epilepticus. The changes on DWI provide an insight into the pathophysiology. We report a 53-year-old man with focal motor status epilepticus involving the left hand, arm and face with focal slowing on EEG. The apparent diffusion coefficients (ADC) were higher in the affected hemisphere than on the other side. At 10 days and 6 weeks after the end of the seizures, we saw normal ADCs and atrophy of the affected hemisphere. We conclude that the MRI findings indicate both cytotoxic and vasogenic oedema during seizure activity and subsequent loss of brain parenchyma. (orig.)

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

    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

  16. Febrile infection-related status epilepticus in a child after a common infection

    Andersen, Anne Helene; Hansen, Lars Kjærsgaard

    2014-01-01

    A 13-year-old boy developed seizures and intractable status epilepticus a week after having had a sore throat. Ketogenic diet possibly had some effect. Antibodies to calmodulin dependent protein kinase II were found and could possibly suggest an immunologic aetiology.......A 13-year-old boy developed seizures and intractable status epilepticus a week after having had a sore throat. Ketogenic diet possibly had some effect. Antibodies to calmodulin dependent protein kinase II were found and could possibly suggest an immunologic aetiology....

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

    Michael E. Reznik

    2016-05-01

    Full Text Available 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.

  18. Refractory Status Epilepticus Due To Cerebral Venous Thrombosis During Late Pregnancy with Successful Outcome

    Kumar S

    2004-01-01

    Full Text Available Status epilepticus complicating pregnancy is uncommon and may be associated with poor maternal and foetal outcome. We report a 24-Year-old lady who presented with refractory status epilepticus at 27 weeks of gestation. The underlying causes identified was extensive was extensive dural cerebral venous sinus thrombosis. She required admission in Neurology intensive car unit and aggressive treatment including mechanical ventilation, anticoagulation and antiepileptic therapy with intravenous phenytoin, & midazolam and thiopentone infusion. She delivered a healthy baby after a spontaneous preterm labour 28 weeks of gestation. At the time of discharge, both mother and child were healthy. A brief literature review is also presented.

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

    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

  20. Status epilepticus ausência de novo: relato de caso "De novo" absence status: case report

    Gloria M. Almeida Tedrus

    1997-09-01

    Full Text Available Existem poucos relatos na literatura de pacientes adultos com status epilepticus não convulsivo, do tipo ausência típica. Apresentamos o caso de paciente do sexo feminino de 53 anos de idade, diabética, que iniciou quadro de confusão mental após crise tônico-clônica generalizada. O eletrencefalograma mostrou descargas contínuas generalizadas caracterizadas por complexos ponta-onda irregulares. As descargas ao eletrencefalograma desapareceram após diazepan endovenoso. A tomografia computadorizada de crânio foi normal. Esse caso mostra que o reconhecimento dessa entidade clínico-eletrencefalográfica é essencial, devido à semelhança com distúrbio psiquiátrico e da pronta resposta ao tratamento medicamentoso.There are few descriptions about middle-aged patients who have nonconvulsive status epilepticus, absence status. We reported the clinical case of a woman, 52-year-old, diabetic, referred to the emergency room in a confusional state. Initial electroencephalogram showed continuous typical, bilateral, symmetric and synchronous spike-and-wave discharges. Clinical and electroencephalogram normalization occurred immediatelly following intravenous injection of benzodiazepine. Computerized axial tomography was normal. The recognition of this entity is essential because of its similarity to psychiatric disturbance and its prompt response to proper treatment.

  1. Inappropriate emergency management of status epilepticus in children contributes to need for intensive care

    Chin, R; Verhulst, L; Neville, B.; Peters, M; Scott, R.

    2004-01-01

    Objectives: To characterise the clinical features, emergency pre-paediatric intensive care (PIC) treatment, and course of status epilepticus (SE) in children admitted to PIC. This may provide insight into reasons for admission to PIC and provide a framework for the development of strategies that decrease the requirement for intensive care.

  2. Treatment of convulsive status epilepticus in the UMCG: A retrospective, observational study

    Vlaskamp, D.R.M.; Brouwer, O.F.; Callenbach, P.M.C.

    2013-01-01

    Objectives: Little is known about clinical practice with respect to the application of guidelines in the treatment of Convulsive Status Epilepticus (CSE). This retrospective, observational study evaluated treatment of episodes of CSE in children at the University Medical Centre Groningen (UMCG). Mat

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

    E.A. van Vliet; W.M. Otte; W.J. Wadman; E. Aronica; G. Kooij; H.E. de Vries; R.M. Dijkhuizen; J.A. Gorter

    2016-01-01

    OBJECTIVE: Blood-brain barrier (BBB) leakage may play a pro-epileptogenic role after status epilepticus. In the accompanying contrast-enhanced magnetic resonance imaging (CE-MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activit

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

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

    2016-01-01

    OBJECTIVE: Blood-brain barrier (BBB) leakage may play a pro-epileptogenic role after status epilepticus. In the accompanying contrast-enhanced magnetic resonance imaging (CE-MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activit

  5. Neuronal degeneration induced by status epilepticus in the nucleus accumens of immature rats

    Druga, Rastislav; Mareš, Pavel; Kubová, Hana

    2007-01-01

    Roč. 48, s6 (2007), s. 19-20. ISSN 0013-9580. [Annual Meeting of the American Epilepsy Society. 31.112007-3.12.2007, Philadelphia] R&D Projects: GA ČR GA304/07/1137 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * neuronal degeneration * status epilepticus * immature rat Subject RIV: FH - Neurology

  6. Thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus: a case report

    Kunii Yasuto

    2011-09-01

    Full Text Available Abstract Introduction Non-convulsive status epilepticus is a form of epileptic seizure that occurs without convulsions. Recent reviews suggest that the diagnosis of non-convulsive status epilepticus remains difficult. Here, we report the case of a patient with thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus. Case presentation Our patient was a 68-year-old Japanese woman. The results of endocrine testing after her first episode of non-convulsive status epilepticus suggested latent subclinical hypothyroidism: she had elevated thyroid-stimulating hormone with normal levels of free tri-iodothyronine and free thyroxine. On examination, a diagnosis of thyroid disorder was not supported by other test results and our patient remained untreated. A follow-up examination revealed that her thyroid-stimulating hormone levels had spontaneously normalized. When she consulted another doctor for confusion, the transient increase in thyroid-stimulating hormone levels following non-convulsive status epilepticus was mistaken for subclinical hypothyroidism, and unfortunately treated with levothyroxine. Our patient then experienced levothyroxine-induced non-convulsive status epilepticus. Conclusions In this report, we suggested possible mechanisms for latent hypothyroid-like hormone abnormality following epileptic seizures and the possibility of provoking epileptic seizures by administering levothyroxine for misdiagnosed subclinical hypothyroidism.

  7. Refractory nonconvulsive status epilepticus in coma: analysis of the evolution of ictal patterns

    Paulo Breno Noronha Liberalesso

    2012-07-01

    Full Text Available OBJECTIVE: Nonconvulsive status epilepticus (NCSE is currently considered as one of the most frequent types of status epilepticus (SE. The objective of the present study was to identify the natural history of the electrographical evolution of refractory NCSE and to establish the relationship between ictal patterns and prognosis. METHODS: We analyzed, retrospectively, 14 patients with loss of consciousness and NCSE. The ictal patterns were classified as discrete seizures (DS, merging seizures (MS, continuous ictal discharges (CID, continuous ictal discharges with flat periods (CID-F, and periodic lateralized epileptiform discharges (PLEDs. RESULTS: The ictal patterns were DS (n=7; 50.0%, PLEDs (n=3; 1.4%, CID (n=2; 14.3%, MS (n=1; 7.1%, and CID-F (n=1; 7.1%. CONCLUSIONS: NCSE electrographic findings are heterogeneous and do not follow a stereotyped sequence. PLEDs were related to a higher probability of neurological morbidity and mortality.

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

    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.

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

    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: 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

  10. Efficacy and Safety of Intravenous Valproate for Status Epilepticus: A Systematic Review

    Trinka, Eugen; Höfler, Julia; Zerbs, Alexander; Brigo, Francesco

    2014-01-01

    Introduction The effectiveness of valproate (VPA) in the treatment of focal and generalized epilepsies is well established. The drug has a wide spectrum of action, good tolerability, and has been available as an injectable formulation since 1993. Despite the lack of class A evidence, it has been used extensively in various forms of status epilepticus (SE). Aim Our aim was to present a systematic review of data from randomized and non-randomized controlled trials to evaluate the efficacy and s...

  11. Treatment of experimental status epilepticus in immature rats: dissociation between anticonvulsant and antiepileptogenic effects

    Suchomelová, Lucie; Baldwin, R. A.; Kubová, Hana; Thompson, K. W.; Sankar, R.; Wasterlain, C. G.

    2006-01-01

    Roč. 59, č. 2 (2006), s. 237-243. ISSN 0031-3998 Grant ostatní: ILAE(BE) Fellowship; Johnson&Johnson´s(US) Pharm. Res. Institute; NINDS(US) NS13515; NINDS(US) NS046516; NINDS(US) NS045911 Institutional research plan: CEZ:AV0Z50110509 Keywords : status epilepticus * treatment * immature rats Subject RIV: ED - Physiology Impact factor: 2.619, year: 2006

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

    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

  13. Analysis on the factors associated with treatment failure of using anesthetics in refractory status epilepticus

    Su, Ying-ying; Guo-ping REN; Wei-bi CHEN; Zhang, Yan; YE Hong; Dai-quan GAO

    2015-01-01

    Objective To analyze the related factors associated with immediate treatment failure of using anesthetics in refractory status epilepticus (RSE).  Methods Thirty patients derived from Neurocritical Care Unit of Xuanwu Hospital from January 2004 to December 2013 were divided into 2 groups (acute treatment failure group and acute treatment success group) based on the treatment outcome 6 h after intravenous injection of anesthetics. Univariate and multivariate forward Logistic regression ...

  14. USE OF INJECTABLE VALPROATE FORMULATIONS IN STATUS EPILEPTICUS IN ADULTS AND CHILDREN

    A. A. Kholin

    2015-01-01

    One of the most actual problems in emergency neurology is therapy of status epilepticus (SE). Antiepileptic drugs used in therapy of SE must be: 1) simple in usage; 2) have rapid action; 3) have prolonged antiepileptic action; 4) demonstrate minimal side effects on cardiorespiratory system and other vital functions. Unfortunately, such drugs traditional used in therapy of SE as benzodiazepines, phenytoin and barbiturates don’t fulfill all this four qualities. Numerous clinical investigations ...

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

    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

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

    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

  17. Contributions of Astrocytes to Epileptogenesis Following Status Epilepticus: Opportunities for Preventive Therapy?

    Gibbons, M.B.; Smeal, R.M.; Takahashi, D.K.; Vargas, J.R.; Wilcox, K.S.

    2012-01-01

    Status epilepticus (SE) is a life threatening condition that often precedes the development of epilepsy. Traditional treatments for epilepsy have been focused on targeting neuronal mechanisms contributing to hyperexcitability, however, approximately 30% of patients with epilepsy do not respond to existing neurocentric pharmacotherapies. A growing body of evidence has demonstrated that profound changes in the morphology and function of astrocytes accompany SE and persist in epilepsy. Astrocyte...

  18. Olfactory and gustatory hallucinations presenting as partial status epilepticus because of glioblastoma multiforme.

    Capampangan, Dan J; Hoerth, Matthew T; Drazkowski, Joseph F; Lipinski, Christopher A

    2010-10-01

    Olfactory and gustatory hallucinations are not often encountered in the acute care setting but may represent the subtle presenting features of a significant underlying disease process. We describe a patient whose most striking presenting symptoms were of olfactory and gustatory hallucinations and in whom the diagnosis and treatment of a new brain tumor and partial status epilepticus occurred entirely in the emergency department. The lesion was subsequently identified as glioblastoma multiforme involving the hippocampus and amygdala. PMID:20303620

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

    Kubová, Hana; Mareš, Pavel

    2013-01-01

    Roč. 235, APR 3 (2013), s. 232-249. ISSN 0306-4522 R&D Projects: GA ČR(CZ) GAP302/10/0971; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) ME08045 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : status epilepticus * immature brain * brain atrophy * epilepsy * cognitive impairment Subject RIV: FH - Neurology Impact factor: 3.327, year: 2013

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

    Tsenov, Grygoriy; Kubová, Hana; Mareš, Pavel

    2008-01-01

    Roč. 78, 2-3 (2008), s. 178-185. ISSN 0920-1211 R&D Projects: GA ČR(CZ) GA309/03/0770; GA ČR(CZ) GA304/05/2582 Institutional research plan: CEZ:AV0Z50110509 Keywords : pilocarpine * status epilepticus * cortical afterdischarges Subject RIV: FH - Neurology Impact factor: 2.405, year: 2008

  1. Study on etiology and treatment of convulsive status epilepticus in children

    Dong LI

    2015-11-01

    Full Text Available The clinical data of 182 children with convulsive status epilepticus (CSE were analyzed. There were 21 cases with refractory status epilepticus (RSE and 161 cases with non-refractory status epilepticus (non-RSE. Etiological factors mainly included epilepsy in 54 cases, intracranial infection in 49 cases, and complex febrile seizure in 44 cases. In the ictal stage, 102 cases were treated with clonazepam by intravenous injection, 54 cases with diazepam by intravenous injection, 46 cases with midazolam by intravenous injection, 36 cases with phenobarbital by muscular injection, and 32 cases with 6.5% chloral hydrate by nosal feeding or clyster. The etiology of CSE in children is various. Epilepsy, intracranial infection and complex febrile seizure are the main causes. Poor prognosis and high mortality often occur in RSE caused by severe viral encephalitis. So the fundamental principle of treatment is to control CSE quickly and avoid the damage of brain and other important organs. DOI: 10.3969/j.issn.1672-6731.2015.11.009

  2. Mitochondrial and nuclear changes in hippocampal neurons in a lithium-pilocarpine-induced status epilepticus rat model

    Shuhai Tang; Li Zhang; Jianying Sun; Xiaojun Pan

    2009-01-01

    BACKGROUND: Mitochondrial damage plays a key role in neuronal damage.OBJECTIVE: To observe ultrastructural damage to mitochondria and nuclei, as well as caspase-3 expression, in hippocampal CA3 neurons of lithium-pilocarpine-induced status epilepticus rats.DESIGN, TIME AND SETTING: The neuropathological, randomized, controlled study was performed at the Animal Experimental Center, Shandong University, China in May 2008.MATERIALS: A total of 75 healthy, adult, male, Wistar rats were randomly assigned into model (n = 45) and control (n = 30) groups. Lithium-pilocarpine (Sigma, USA) was used in this study.METHODS: Rats in the model group were intraperitoneally injected with lithium chloride (3 mEq/kg),and 24 hours later with pilocarpine (45 mg/kg), to induce seizures for 2 hours. Rats in the control group were intraperitoneally infused with the same volume of saline. Rat hippocampal CA3 tissue was obtained at 3, 12, and 24 hours following status epilepticus.MAIN OUTCOME MEASURES: Neuronal changes were observed under an optical microscope. Ultrastructural changes in mitochondria and nuclei were observed using an electron microscope.caspase-3 mRNA levels were quantified by semiquantitative RT-PCR.RESULTS: After 3 hours of status epilepticus, mitochondria with swollen cristae and ruptured membranes were observed by electron microscopy. Nuclei with marginated chromatin were observed after 24 hours status epilepticus. RT-PCR results demonstrated increased caspase-3 expression at 12 hours, and significantly increased expression at 24 hours following termination of status epilepticus. This was in accordance with acidophilia occurrence, as indicated by hematoxylin-eosin staining, and time of ultrastructural damage to nuclei.CONCLUSION: In lithium-pilocarpine-induced status epilepticus rat models, ultrastructural damage to mitochondria in hippocampal neurons occurred during early stages, followed by increased caspase-3 expression and nuclear changes. These results suggested

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

    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

  4. Complex partial non-convulsive status epilepticus masquerading as hepatic encephalopathy: a case report

    Badshah Maaz B

    2012-12-01

    Full Text Available Abstract Introduction Hepatic encephalopathy is usually suspected in patients who are cirrhotic with neuropsychiatric manifestations. We present a case of suspected hepatic encephalopathy that did not respond to standard empiric therapy and was eventually diagnosed as non-convulsive status epilepticus of complex partial type. Our patient responded dramatically to anti-convulsive therapy. Case presentation We report the case of a 45-year-old African-American man with hepatitis C virus cirrhosis and human immunodeficiency virus who presented to our facility with a one-day history of confusion and a variable mental status. Our patient’s vital signs were stable and all his electrolytes were within normal range. A clinical diagnosis of hepatic encephalopathy was made and our patient was started on empiric therapy with lactulose and rifaximin. Our patient did not respond to therapy. After five days of treatment, alternative diagnoses were sought and a neurology consult was requested. An electroencephalogram was eventually performed which showed seizure activity in the right parietal lobe. A diagnosis of non-convulsive status epilepticus was made and our patient was started on oral levetiracetam. On day two of therapy, our patient was alert and oriented. He continues to do well on follow-up approximately one year after discharge. Conclusions Non-convulsive status epilepticus should be considered in the differential diagnosis of patients with suspected hepatic encephalopathy who do not respond to empirical treatment. Further studies are needed to investigate the incidence of this entity in patients with persistent hepatic encephalopathy.

  5. MicroRNAs in the pathophysiology and treatment of status epilepticus

    David Henshall

    2013-11-01

    Full Text Available MicroRNAs are an important class of non-coding RNA which function as post-transcriptional regulators of gene expression in cells, repressing and fine-tuning protein output. Prolonged seizures (status epilepticus, SE can cause damage to brain regions such as the hippocampus and result in cognitive deficits and the pathogenesis of epilepsy. Emerging work in animal models has found that SE produces select changes to microRNAs within the brain. Similar changes in over 20 microRNAs have been found in the hippocampus in two or more studies, suggesting conserved microRNA responses after SE. The microRNA changes that accompany SE are predicted to impact levels of multiple proteins involved in neuronal morphology and function, gliosis, neuroinflammation and cell death. MicroRNA expression also displays select changes in the blood after SE, supporting blood genomic profiling as potential molecular biomarkers of seizure-damage or epileptogenesis. Intracerebral delivery of chemically-modified antisense oligonucleotides (antagomirs has been shown to have potent, specific and long-lasting effects on brain levels of microRNAs. Targeting miR-34a, miR-132 and miR-184 has been reported to alter seizure-induced neuronal death, whereas targeting miR-134 was neuroprotective, reduced seizure severity during status epilepticus and reduced the later emergence of recurrent spontaneous seizures. These studies support roles for microRNAs in the pathophysiology of status epilepticus and microRNAs may represent novel therapeutic targets to reduce brain injury and epileptogenesis.

  6. Efficacy and Safety of Intravenous Sodium Valproate in Convulsive Status Epilepticus in Children in Shahid Sadoughi Hospital

    Razieh FALLAH

    2012-06-01

    Full Text Available How to Cite this Article: Fallah R, Yadegari Y, Salmani Nodushan M. Efficacy and Safety of Intravenous Sodium Valproate in Convulsive Status Epilepticus in Children in Shahid Sadoughi Hospital. Iran. J. Child. Neurol 2012;6(2:39-44. Objective Status epilepticus (SE is the most common pediatric neurologic emergency with high mortality and morbidity. There is no consensus on the drug of choice in the treatment of children. The purpose of this study was to evaluate the clinical efficacy and safety of intravenous sodium valproate as a third-line drug in the treatment of generalized convulsive SE of children. Materials & Methods In a retrospective study, medical records of those children who were admitted to Shahid Sadoughi Hospital of Yazd due to refractory generalized convulsive SE and were treated by intravenous sodium valproate as a third-line drug from 2009 to 2011 were evaluated. Results Six girls and five boys with a mean age of 5.12 ± 1.2 years (range: 3 - 9.6 years were evaluated. Intravenous valproate was effective for cessation of seizures in seven patients (63.6 %. The mean dose of valproate for stopping seizures was 27.1 ± 1.4 mg/kg/day. Children whose seizures were controlled by sodium valproate were older than non- responsive children (mean± SD: 4.8 ± 1.2 years vs. 3.1 ± 0.43 years, p= 0.03 and they also had shorter ICU stay days (mean± SD: 2.6 ± 1.4 days vs. 5.6 ± 2.8 days, p= 0.01. Two children had mild and transient nausea and vomiting. None of them had cardiopulmonary or severe paraclinical side effects. Conclusion Intravenous sodium valproate may be used as an effective and safe third-line antiepileptic drug in the treatment of pediatric generalized convulsive status epilepticus.References Raj D, Gulati S, Lodha R. Status epilepticus. Indian J Pediatr 2011;78(2:219-26. Shearer P, Riviello J. Generalized convulsive status epilepticus in adults and children: treatment guidelines and protocols. Emerg Med Clin North Am 2011

  7. Diagnosis and interpretation of EEG on non-convulsive status epilepticus

    Xiao-gang KANG

    2015-11-01

    Full Text Available It is difficult to diagnose non-convulsive status epilepticus (NCSE clinically because of the complicated etiology and various clinical and electroencephalographic features of NCSE without a universally accepted definition. Although the diagnosis of NCSE relies largely on electroencephalogram (EEG findings, the determination of NCSE on EEG is inevitably subjective, and the EEG changes of most patients is lack of specificity. As the diagnosis of NCSE is related to clinical and electroencephalographic manifestations, diagnostic criteria for NCSE should take into account both clinical and electroencephalographic features, and their response to antiepileptic drugs (AEDs. DOI: 10.3969/j.issn.1672-6731.2015.11.005

  8. p75NTR, but Not proNGF, Is Upregulated Following Status Epilepticus in Mice

    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 p75NTR 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 p75NTR, sortilin, and sorCS2, following mild SE induced with kainic acid (KA) or severe SE induced by pilocarpine. We found that m...

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

    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

  10. Status Epilepticus Due to Severe HHV-6 Encephalitis in an Allogeneic Stem Cell Transplant Recipient

    Poorvi Chordia

    2013-12-01

    Full Text Available Reactivation of human herpes virus-6 (HHV-6 after stem cell transplantation occurs frequently. It is associated with clinical manifestations varying from nonspecific symptoms such as fevers or rash, to severe life threatening complications including post-transplantation limbic encephalitis. We report a case of severe HHV-6 encephalitis with viremia in an allogeneic peripheral stem cell transplant recipient who presented with status epilepticus unresponsive to antiepileptic therapy.  With intravenous ganciclovir and supportive care, the patient’s condition improved. Awareness of HHV-6 infection in stem cell transplant recipients may help with early diagnosis and improved outcome.

  11. Slow pseudoperiodic lateralized epileptiform discharges in nonconvulsive status epilepticus in a patient with cerebral palsy and a large central meningioma

    Y.Z. Imam

    2014-01-01

    Full Text Available The presence of cerebral palsy and that of slow growing brain tumors are risk factors for convulsive and nonconvulsive status epilepticus. Nonconvulsive status epilepticus (NCSE needs electroencephalographic (EEG monitoring to be confirmed as it may be clinically subtle. Furthermore, it may present with a variety of ictal EEG morphologies. We report a case of a patient with cerebral palsy and a large central meningioma. Electroencephalogram showed a slow pattern of periodic lateralized epileptiform discharges (PLEDs (a pattern considered as being situated in the ictal–interictal continuum on an alpha background. The patient was treated for NCSE successfully with benzodiazepines followed by up-titration of his antiepileptic drug doses.

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

    Gentle Sunder Shrestha

    2015-01-01

    Full Text Available 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.

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

    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

  14. Glucose utilisation during status epilepticus in an epilepsy model induced by pilocarpine: a qualitative study

    Scorza Fulvio Alexandre

    2002-01-01

    Full Text Available Status epilepticus (SE is a medical emergency and it is associated to brain damage. 2-deoxy-[14C] glucose (2-DG procedure has been used to measure the alterations in the functional activity of the brain induced by various pharmacological and toxicological agents. The aim of this study was to determine which changes occur in the seizure anatomic substrates during the SE induced by pilocarpine (PILO using [14C]-2 deoxyglucose functional mapping technique. Wistar male adult rats were submitted to SE PILO-induced for 6h and received [14C] 2-deoxyglucose injection via jugular vein 45 min before the 6th hour of SE. The control animals were submitted to all procedures but received saline and not pilocarpine. Brain sections were prepared and exposed X-ray film about seven days. The optical density of each region was obtained using a solid state digital analyser. The analysis revealed that 14C-2DG utilisation was pronounced in the SE rats on the areas corresponding to the hippocampal formation (+50.6%, caudate-putamen (+30.6%, frontoparietal cortex (+32.2%, amygdala (+31.7%, entorrinal cortex (+28.2%, thalamic nucleus (+93.5%, pre-tectal area (+50.1% and substantia nigra (+50.3% when compared to control. Our results suggest that the different activation levels of the distinct structures may be particularly important for understanding triggering and spreading mechanisms underlying epileptic activity during status epilepticus.

  15. Analysis of factors influencing admission to intensive care following convulsive status epilepticus in children.

    Tirupathi, Sandya

    2012-02-01

    OBJECTIVES: To identify clinical features and therapeutic decisions that influence admission to the Intensive Care unit (ICU) in children presenting with convulsive status epilepticus (CSE). METHODS: We evaluated 47 admissions with status epilepticus to a tertiary paediatric hospital A&E over a three year period (2003-2006). Following initial management 23 episodes required admission to ICU and 24 were managed on a paediatric ward. We compared clinical, demographic data and compliance with our CSE protocol between the ICU and ward groups. RESULTS: Median age at presentation in the ICU group was 17 months (range 3 months-11 years) compared to 46 months in the ward group (range 3 months-10 years). Fifty per cent of patients in both groups had a previous history of seizures. Median duration of pre-hospital seizure activity was 30 min in both groups. More than two doses of benzodiazepines were given as first line medication in 62% of the ICU group and 33% of the ward group. Among children admitted to ICU with CSE, 26% had been managed according to the CSE protocol, compared to 66% of children who were admitted to a hospital ward. Febrile seizures were the most common aetiology in both groups. CONCLUSION: Younger age at presentation, administration of more than two doses of benzodiazepines and deviation from the CSE protocol appear to be factors which influence admission of children to ICU. Recognition of pre-hospital administration of benzodiazepines and adherence to therapeutic guidelines may reduce the need for ventilatory support in this group.

  16. A Case Of Primary Central Nervous System Vasculitis Who Presented With Status Epilepticus

    Sırma Geyik

    2014-12-01

    Full Text Available Primary central nervous system vasculitis (PCNV is limited with central nervous system and rare vasculitis that mostly seen in middle-aged men. PCNV vasculitis is usually presented that headache, dementia, stroke and multifocal common neurological symptoms. PCNV especially involves small medium-sized leptomeningeal and cortical arteries. 43 years old male patient who have been progressive forgetfulness and headache for 3 years. He applied with recurrent that before starting right focal and than sprawling whole body which generalized tonic-clonic seizures to us. During management that he was transfered to the intensive care unit due to status epilepticus (SE. Later than we found right hemiparesis, motor aphasia and right babinski positivity in neurologic examination. Diffusion restriction was revealed in left MCA territory in diffusion magnetic resonance imaging(MRI. EEG showed two types abnormality that a slow background ritm and epileptiform activity. Biochemistry of blood, complete blood count, blood sedimentation rate, CRP and markers of vasculitis were found in the normal range. Cerebral anjiography revealed that irregularities in the distal vascular areas and fusiform aneurysm at the top of basilar artery. He was consulted with rheumatology and diagnosed central nervous system vasculitis with the existing findings. Biopsy couldn't be taken from the brain to verify the diagnosis. Finally, we applied treatment that pulse steroid and cyclophosphamide to patient. This case has been presented due to emphasize that PCNV rarely may play a role in the etiology of recurrent stroke and status epilepticus.

  17. Impact of the NCAM derived mimetic peptide plannexin on the acute cellular consequences of a status epilepticus

    Zellinger, Christina; Hadamitzky, Martin; Bock, Elisabeth;

    2011-01-01

    hippocampal subregions. The comparison between the vehicle- and plannexin-treated animals with status epilepticus did not reveal neuroprotective effects of plannexin on mature neurons. However, treatment with plannexin partially prevented the reduction in the number of doublecortin-labeled neuronal progenitor...

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

    Druga, R.; Mareš, Pavel; Kubová, Hana

    2010-01-01

    Roč. 1355, - (2010), s. 174-176. ISSN 0006-8993 R&D Projects: GA ČR GA304/04/0464; GA ČR(CZ) GA304/07/1137 Institutional research plan: CEZ:AV0Z50110509 Keywords : degenerating neurons * status epilepticus * ontogeny Subject RIV: FH - Neurology Impact factor: 2.623, year: 2010

  19. The CNTF-derived peptide mimetic Cintrofin attenuates spatial-learning deficits in a rat post-status epilepticus model

    Russmann, Vera; Seeger, Natalie; Zellinger, Christina; Hadamitzky, Martin; Pankratova, Stanislava; Wendt, Hannes; Bock, Elisabeth; Berezin, Vladimir; Potschka, Heidrun

    2013-01-01

    Ciliary neurotrophic growth factor is considered a potential therapeutic agent for central nervous system diseases. We report first in vivo data of the ciliary neurotrophic growth factor peptide mimetic Cintrofin in a rat post-status epilepticus model. Cintrofin prevented long-term alterations in...

  20. Transcriptional response of polycomb group genes to status epilepticus in mice is modified by prior exposure to epileptic preconditioning

    James eReynolds

    2015-03-01

    Full Text Available Exposure of the brain to brief, non-harmful seizures can activate protective mechanisms that temporarily generate a damage-refractory state. This process, termed epileptic tolerance, is associated with large-scale down-regulation of gene expression. Polycomb group proteins are master controllers of gene silencing during development that are re-activated by injury to the brain. Here we explored the transcriptional response of genes associated with polycomb repressor complex (PRC 1 (Ring1A and Ring1B and Bmi1 and PRC2 (Ezh1, Ezh2 and Suz12, as well as additional transcriptional regulators Sirt1, Yy1 and Yy2, in a mouse model of status epilepticus. Findings were contrasted to changes after status epilepticus in mice previously given brief seizures to evoke tolerance. Real-time quantitative PCR showed status epilepticus prompted an early (1 h increase in expression of several genes in PRC1 and PRC2 in the hippocampus, followed by down-regulation of many of the same genes at later times points (4 , 8 and 24 h. Spatio-temporal differences were found among PRC2 genes in epileptic tolerance, including increased expression of Ezh2, Suz12 and Yy2 relative to the normal injury response to status epilepticus. In contrast, PRC1 complex genes including Ring 1B and Bmi1 displayed differential down-regulation in epileptic tolerance. The present study characterizes polycomb group gene expression following status epilepticus and shows prior seizure exposure produces select changes to PRC1 and PRC2 composition that may influence differential gene expression in epileptic tolerance.

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

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

    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 epile...

  2. Pilocarpine-induced status epilepticus in rats involves ischemic and excitotoxic mechanisms.

    Paolo Francesco Fabene

    Full Text Available 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.

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

    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

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

    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

  5. Status epilepticus associated with initiation of theophylline in an elderly patient with diabetic ketoacidosis

    Chung-Hsing Chou

    2007-01-01

    Full Text Available An 80-year-old man with a history of Type 2 diabetes mellitus was hospitalized due to generalized convulsive status epilepticus. Initially, hyperglycemia and ketoacidosis were diagnosed, but his seizures were refractory to the medical treatment. Additionally, a high level of serum theophylline (29.1 mg/mL was detected. Following detoxification of theophylline by oral activated charcoal, the patient regained consciousness and was free from seizures without antiepileptic drug treatment. Brain magnetic resonance imaging revealed subacute subdural hematomas at the bilateral occipital hemispheres. This case suggests that theophylline toxicity may be a predisposing factor for seizures in patients with a history of traumatic brain injury in spite of the presence of diabetic ketoacidosis that may have an anticonvulsant action.

  6. Combined use of intravenous anesthetics and hypothermia in treating refractory status epilepticus

    Guo-ping REN

    2015-11-01

    Full Text Available The primary choice of treating refractory status epilepticus (RSE is intravenous anesthetics, but the seizures of some patients can not get a good control. Thus, other therapies must be combined. Hypothermia not only can terminate seizures, but also play a part in brain protection. Though combined use of intravenous anesthetics and hypothermia is not a regular clinical scheme, the favorable effect has been proved by a lot of clinical research. This paper mainly focuses on the dose of intravenous anesthetics, the time, temperature and procedure of hypothermia, the indications and contraindications of combined therapy, and so on. DOI: 10.3969/j.issn.1672-6731.2015.11.006

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

    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

  8. Opercular myoclonic-anarthric status epilepticus: A report of two cases

    Janapareddy Vijaya Bhaskara Rao

    2013-01-01

    Full Text Available Opercular myoclonic-anarthric status epilepticus (OMASE is an uncommon disorder of diverse etiology. This condition is characterized by fluctuating cortical dysarthria associated with epileptic myoclonus involving glossopharyngeal musculature bilaterally. We report two cases of OMASE of vascular etiology in adults. In both patients, ictally clonic expression was consistent with epilepsia partialis continua and bilateral, symmetrical involvement of soft palate in one patient and tongue, lips, chin and inferior jaw in both patients due to bilateral projections of the inferior corticonuclear pathways. The inferior rolandic area of dominant and high frontal region in non-dominant hemispheres were involved by an epileptogenic lesion of vascular etiology, which was confirmed by magnetic resonance imaging of brain and single photon emission computerized tomography. Carotid Doppler study showed thrombosis of internal carotid artery in both patients, suggestive of an embolic origin. Early recognition of OMASE is important for early management of carotid occlusive disease.

  9. Analysis on the factors associated with treatment failure of using anesthetics in refractory status epilepticus

    Ying-ying SU

    2015-11-01

    Full Text Available Objective To analyze the related factors associated with immediate treatment failure of using anesthetics in refractory status epilepticus (RSE.  Methods Thirty patients derived from Neurocritical Care Unit of Xuanwu Hospital from January 2004 to December 2013 were divided into 2 groups (acute treatment failure group and acute treatment success group based on the treatment outcome 6 h after intravenous injection of anesthetics. Univariate and multivariate forward Logistic regression analyses were used to analyze and screen the risk factors associated with immediate treatment failure, and calculate the failure rate of final outcome.  Results According to the results of univariate and multivariate Logistic regression analyses, among influencing factors such as sex, age, etiology, Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ, type of status epilepticus (SE, type of antiepileptic drugs (AEDs, total duration of primary treatment, duration of prehospital primary treatment, duration of posthospital primary treatment, type of RSE and primary choice of anesthetics, only total duration of primary treatment was the independent risk factor for immediate treatment failure (OR = 1.007, 95%CI: 1.000-1.014; P = 0.047. The rate of immediate treatment failure of RSE by using anesthetics was 50% (15/30, and the rate of final treatment failure was 43.33% (13/30. The ratio of final treatment failure was much higher in acute treatment failure group than that in acute treatment success group (10/15 vs 3/15, P = 0.025.  Conclusions The acute treatment result of RSE depends on the total duration of primary treatment, and determinates the final result of treatment. On the basis of treating primary disease, the therapy to terminate SE or RSE should be started as early as possible. DOI: 10.3969/j.issn.1672-6731.2015.11.008

  10. Effects of LiCl/PILOCARPINE-induced status epilepticus on rat brain benzodiazepine receptor binding: regional and ontogenetic study

    Kubová, Hana; Suchomelová, Lucie; Rocha, L.

    Praha : The Czech Neuroscience Society, 2007. s. 32-32. [Conference of the Czech Neuroscience Society /6./. 19.11.2007-20.11.2007, Praha] R&D Projects: GA ČR(CZ) GA304/05/2582; GA ČR(CZ) GD305/03/H148 Grant ostatní: CONACyT(MX) 45943-M Institutional research plan: CEZ:AV0Z50110509 Keywords : spr2 * status epilepticus * LiCl/pilocarpine * ontogeny Subject RIV: FH - Neurology

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

    Pugin, Deborah; Foreman, Brandon; De Marchis, Gian Marco; Fernandez, Andres; Schmidt, J. Michael; Czeisler, Barry M; Mayer, Stephan A; Agarwal, Sachin; Lesch, Christine; Lantigua, Hector; Claassen, Jan

    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...

  12. Free radical scavenger, N-tert-butyl-alfa-phenylnitrone, affects long-term outcome of status epilepticus in immature rats

    Kubová, Hana; Rejchrtová, Jana; Folbergrová, Jaroslava; Mareš, Pavel

    2005-01-01

    Roč. 46, č. S8 (2005), s. 111-112. [Joint Annual Meeting of the American Epilepsy Society and American Clinical Neurophysiology Society. 02.12.2005-06.12.2005, Washington, DC] R&D Projects: GA ČR(CZ) GA304/05/2582 Institutional research plan: CEZ:AV0Z50110509 Keywords : status epilepticus * PBN * rat Subject RIV: ED - Physiology

  13. Kontinuierliche EEG Überwachung für die Therapie von Hunden und Katzen im Status epilepticus

    Raith, Karina

    2010-01-01

    Goal of this case series was to describe the management of Status epilepticus in dogs and cats with the aid of continuous electroencephalographic (EEG) monitoring. Ten patients (7 dogs, 3 cats) with SE of differing etiology (idiopathic epilepsy, n=3; toxicity, n=4; meningoencephalitis, n=2; undefined, n=1) were included in the study. The EEG was recorded continuously from five stainless steel needle-electrodes inserted subcutaneously. Animals were treated with diazepam and phenobarbital follo...

  14. Loss of p53 results in protracted electrographic seizures and development of an aggravated epileptic phenotype following status epilepticus

    Engel, T.; K.Tanaka; Jimenez-Mateos, E M; Caballero-Caballero, A; Prehn, J. H. M.; HENSHALL, D. C.

    2010-01-01

    The p53 tumor suppressor is a multifunctional protein, which regulates cell cycle, differentiation, DNA repair and apoptosis. Experimental seizures up-regulate p53 in the brain, and acute seizure-induced neuronal death can be reduced by genetic deletion or pharmacologic inhibition of p53. However, few long-term functional consequences of p53 deficiency have been explored. Here, we investigated the development of epilepsy triggered by status epilepticus in wild-type and p53-deficient mice. Ana...

  15. P2X7 receptor-mediated PARP1 activity regulates astroglial death in the rat hippocampus following status epilepticus

    Ji-Eun Kim

    2015-01-01

    Poly(ADP-ribose) polymerase-1 (PARP1) plays a regulatory role in apoptosis, necrosis, and other cellular processes after injury. Recently, we revealed that PARP1 regulates the differential neuronal/astroglial responses to pilocarpine-induced status epilepticus (SE) in the distinct brain regions. In addition, P2X7 receptor (P2X7R), an ATP-gated ion channel, activation accelerates astroglial apoptosis, while it attenuates clasmatodendrosis (lysosome-derived autophagic astroglial death). Therefo...

  16. Valnoctamide enhances phasic inhibition: a potential target mechanism for the treatment of benzodiazepine-refractory status epilepticus

    Spampanato, Jay; Dudek, F. Edward

    2014-01-01

    Valnoctamide (VCD), a derivative of valproate, suppresses electrographic seizures in animal models of status epilepticus (SE), even when the seizures are resistant to benzodiazepines (BZDs). We therefore tested the effect of VCD on miniature inhibitory post-synaptic currents (mIPSCs) in CA1 pyramidal cells to determine if VCD acts directly on GABAA receptors. Bath-applied VCD induced a specific, rapid, dose-dependent, and reversible slowing of the decay of mIPSCs (i.e., increased time constan...

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

    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

  18. The potential of sec-butylpropylacetamide (SPD) and valnoctamide and their individual stereoisomers in status epilepticus.

    Shekh-Ahmad, Tawfeeq; Mawasi, Hafiz; McDonough, John H; Yagen, Boris; Bialer, Meir

    2015-08-01

    sec-Butylpropylacetamide (SPD) is a one-carbon homologue of valnoctamide (VCD), a chiral constitutional isomer of valproic acid's (VPA) corresponding amide--valpromide. Racemic-SPD and racemic-VCD possess a unique and broad-spectrum antiseizure profile superior to that of VPA. In addition, SPD blocks behavioral and electrographic status epilepticus (SE) induced by pilocarpine and the organophosphates soman and paraoxon. Valnoctamide has similar activity as SPD in the soman-induced SE model. The activity of SPD and VCD against SE is superior to that of diazepam and midazolam in terms of rapid onset, potency, and ability to block SE when given 20 to 60 min after seizure onset. sec-Butylpropylacetamide and VCD possess two stereogenic carbons in their chemical structure and, thus, exist as a racemic mixture of four individual stereoisomers. The anticonvulsant activity of the individual stereoisomers of SPD and VCD was comparatively evaluated in several anticonvulsant rodent models including the benzodiazepine-resistant SE model. sec-Butylpropylacetamide has stereoselective pharmacokinetics (PK) and pharmacodynamics (PD). The higher clearance of (2R,3S)-SPD and (2S,3R)-SPD led to a 50% lower plasma exposure and, consequently, to a lower anticonvulsant activity compared to racemic-SPD and its two other stereoisomers. Racemic-SPD, (2S,3S)-SPD, and (2R,3R)-SPD have similar anticonvulsant activities and PK profiles that are better than those of (2R,3S)-SPD and (2S,3R)-SPD. Valnoctamide has a stereoselective PK with (2S,3S)-VCD exhibiting the lowest clearance and, consequently, a twice-higher plasma exposure than all other stereoisomers. Nevertheless, there was less stereoselectivity in VCD anticonvulsant activity, and each stereoisomer had similar ED50 values in most models. sec-Butylpropylacetamide and VCD stereoisomers did not cause teratogenicity (i.e., neural tube defect) in mice at doses 3-12 times higher than their anticonvulsant-ED50 values. This article is part of a

  19. Mechanisms of levetiracetam in the control of status epilepticus and epilepsy

    Laxmikant S Deshpande

    2014-01-01

    Full Text Available Status epilepticus (SE is a major clinical emergency that is associated with high mortality and morbidity. SE causes significant neuronal injury and survivors are at a greater risk of developing acquired epilepsy and other neurological morbidities, including depression and cognitive deficits. Benzodiazepines and some anticonvulsant agents are drugs of choice for initial SE management. Despite their effectiveness, over 40% of SE cases are refractory to the initial treatment with two or more medications. Thus there is an unmet need of developing newer anti-SE drugs. Levetiracetam (LEV is a widely prescribed anti-epileptic drug that has been reported to be used in SE cases, especially in benzodiazepine-resistant SE or where phenytoin cannot be used due to allergic side-effects. Levetiracetam’s non-classical antiepileptic mechanisms of action, favorable pharmacokinetic profile, general lack of central depressant effects and lower incidence of drug interactions contributes to its use in SE management. This review will focus on LEV’s unique mechanism of action that makes it a viable candidate for SE treatment.

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

    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

  1. Focal hemodynamic patterns of status epilepticus detected by susceptibility weighted imaging (SWI)

    Aellen, Jerome; Kottke, Raimund; Springer, Elisabeth; Weisstanner, Christian; El-Koussy, Marwan; Schroth, Gerhard; Wiest, Roland; Gralla, Jan; Verma, Rajeev K. [University of Bern, University Institute for Diagnostic and Interventional Neuroradiology, University Hospital Bern and Inselspital, Bern (Switzerland); Abela, Eugenio; Schindler, Kaspar [University of Bern, Department of Neurology, Inselspital, Bern (Switzerland); Buerki, Sarah E. [Inselspital, Department of Neuropaediatrics, University Children' s Hospital, Bern (Switzerland)

    2014-11-15

    To investigate pathological findings in the susceptibility weighted imaging (SWI) of patients experiencing convulsive (CSE) or non-convulsive status epilepticus (NCSE) with focal hyperperfusion in the acute setting. Twelve patients (six with NCSE confirmed by electroencephalogram (EEG) and six patients with CSE with seizure event clinically diagnosed) underwent MRI in this acute setting (mean time between onset of symptoms and MRI was 3 h 8 min), including SWI, dynamic susceptibility contrast MR imaging (DSC) and diffusion-weighted imaging (DWI). MRI sequences were retrospectively evaluated and compared with EEG findings (10/12 patients), and clinical symptoms. Twelve out of 12 (100 %) patients showed a focal parenchymal area with pseudo-narrowed cortical veins on SWI, associated with focal hyperperfused areas (increased cerebral blood flow (CBF) and mean transit time (MTT) shortening), and cortical DWI restriction in 6/12 patients (50 %). Additionally, these areas were associated with ictal or postical EEG patterns in 8/10 patients (80 %). Most frequent acute clinical findings were aphasia and/or hemiparesis in eight patients, and all of them showed pseudo-narrowed veins in those parenchymal areas responsible for these symptoms. In this study series with CSE and NCSE patients, SWI showed focally pseudo-narrowed cortical veins in hyperperfused and ictal parenchymal areas. Therefore, SWI might have the potential to identify an ictal region in CSE/NCSE. (orig.)

  2. Focal hemodynamic patterns of status epilepticus detected by susceptibility weighted imaging (SWI)

    To investigate pathological findings in the susceptibility weighted imaging (SWI) of patients experiencing convulsive (CSE) or non-convulsive status epilepticus (NCSE) with focal hyperperfusion in the acute setting. Twelve patients (six with NCSE confirmed by electroencephalogram (EEG) and six patients with CSE with seizure event clinically diagnosed) underwent MRI in this acute setting (mean time between onset of symptoms and MRI was 3 h 8 min), including SWI, dynamic susceptibility contrast MR imaging (DSC) and diffusion-weighted imaging (DWI). MRI sequences were retrospectively evaluated and compared with EEG findings (10/12 patients), and clinical symptoms. Twelve out of 12 (100 %) patients showed a focal parenchymal area with pseudo-narrowed cortical veins on SWI, associated with focal hyperperfused areas (increased cerebral blood flow (CBF) and mean transit time (MTT) shortening), and cortical DWI restriction in 6/12 patients (50 %). Additionally, these areas were associated with ictal or postical EEG patterns in 8/10 patients (80 %). Most frequent acute clinical findings were aphasia and/or hemiparesis in eight patients, and all of them showed pseudo-narrowed veins in those parenchymal areas responsible for these symptoms. In this study series with CSE and NCSE patients, SWI showed focally pseudo-narrowed cortical veins in hyperperfused and ictal parenchymal areas. Therefore, SWI might have the potential to identify an ictal region in CSE/NCSE. (orig.)

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

    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

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

    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

  5. Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.

    Inna Sukhotinsky

    Full Text Available Epilepsy is a devastating disease, currently treated with medications, surgery or electrical stimulation. None of these approaches is totally effective and our ability to control seizures remains limited and complicated by frequent side effects. The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats. Hippocampal pyramidal neurons were transduced in vivo with a virus carrying an enhanced halorhodopsin (eNpHR, a yellow light activated chloride pump, and acute seizure progression was then monitored behaviorally and electrophysiologically in the presence and absence of illumination delivered via an optical fiber. Inhibition of those neurons with illumination prior to seizure onset significantly delayed electrographic and behavioral initiation of status epilepticus, and altered the dynamics of ictal activity development. These results reveal an essential role of hippocampal excitatory neurons in this model of ictogenesis and illustrate the power of optogenetic approaches for elucidation of seizure mechanisms. This early success in controlling seizures also suggests future therapeutic avenues.

  6. Status Epilepticus as a Presenting Sign of Reversible Posterior Leukoencephalopathy Syndrome in a Liver Transplant Recipient

    Seyed-Mohammadali Musavi

    2009-03-01

    Full Text Available Background: Reversible posterior leukoencephalopathy syndrome (RPLE is an increasingly recognized disorder, most commonly associated with immunosuppressive and cytotoxic agent, malignant hypertension and toxemia of pregnancy. Neurological symptoms are headache, mental and visual disturbance, and seizures. Brain MRI findings are symmetrical bilateral hyper intense areas of occipital and parietal lobes in T2-weighted magnetic resonance (MR images. This finding is reversible with prompt successful treatment which may take days to weeks for full reversal. Case Presentation: We observed a case of status epilepticus which occurred 32 days after liver transplantation in a patient on regimen consisting of Tacrolimus (FK 506. He had no history of neurologic disease or metabolic abnormalities. Typical findings of RPLE were present on brain MRI. The recurrence of seizures terminated after a few hours with adding Na-valproate to Phenytoin, Phenobarbital and Midazolam. The radiological finding of brain MRI gradually diminished after several weeks. Conclusion: A physician should be alert of seizures during early post transplant period of liver transplantation. He should bear in mind the diagnosis of RPLE and consider discontinuation of immunosuppressive drugs.

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

    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

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

    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

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

    Mounira Sabilallah

    Full Text Available 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.

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

    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

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

    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

  12. Peri-ictal signal changes in seven patients with status epilepticus: interesting MRI observations

    Goyal, Manoj K.; Sinha, Sanjib [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neurology, Bangalore, Karnataka (India); Ravishankar, Shivshankar; Shivshankar, Jai Jai [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neuroimaging and Interventional Radiology, Bangalore (India)

    2009-03-15

    Transient peri-ictal changes on imaging had been described following status epilepticus (SE), but its cause is not very well understood. We analyzed the magnetic resonance imaging (MRI) findings in SE patients in order to elucidate such changes including peri-ictal signal. This prospective study involved 34 patients (M/F 23:11, mean age 25.8 {+-} 17.2 years) who experienced SE. MRI was performed during or within 96 h of cessation of seizures. Twenty-five patients had generalized convulsive status epilectus (GCSE; ten secondary GCSE and 15 primary GCSE). Seven patients had epilepsia partialis continua and two patients non-convulsive SE. Eight patients had a history of seizures and three patients previous SE. The mean duration of SE prior to MRI was 89.2 {+-} 105.3 h (range 2-360 h). MRI provided diagnosis in 17 patients, and in 13 patients, no structural cause was identified. Peri-ictal focal signal changes with restricted diffusion on apparent diffusion coefficient maps were present in seven (20.6%) patients with SE (generalized convulsive, three; partial, three; non-convulsive, one). The changes were observed when MRI was performed during SE in 3/10 (30%) patients, or within 24 h in 1/7 (14.3%), 48 h in 1/5 (20%), 72 h in 1/6 (16.7%), or 96 h in 1/6 (16.7%) patients after cessation of seizures. Repeat MRI revealed disappearance of signal changes in two patients. Peri-ictal MR changes with restricted diffusion appear to be an effect rather than the cause of SE. (orig.)

  13. Peri-ictal signal changes in seven patients with status epilepticus: interesting MRI observations

    Transient peri-ictal changes on imaging had been described following status epilepticus (SE), but its cause is not very well understood. We analyzed the magnetic resonance imaging (MRI) findings in SE patients in order to elucidate such changes including peri-ictal signal. This prospective study involved 34 patients (M/F 23:11, mean age 25.8 ± 17.2 years) who experienced SE. MRI was performed during or within 96 h of cessation of seizures. Twenty-five patients had generalized convulsive status epilectus (GCSE; ten secondary GCSE and 15 primary GCSE). Seven patients had epilepsia partialis continua and two patients non-convulsive SE. Eight patients had a history of seizures and three patients previous SE. The mean duration of SE prior to MRI was 89.2 ± 105.3 h (range 2-360 h). MRI provided diagnosis in 17 patients, and in 13 patients, no structural cause was identified. Peri-ictal focal signal changes with restricted diffusion on apparent diffusion coefficient maps were present in seven (20.6%) patients with SE (generalized convulsive, three; partial, three; non-convulsive, one). The changes were observed when MRI was performed during SE in 3/10 (30%) patients, or within 24 h in 1/7 (14.3%), 48 h in 1/5 (20%), 72 h in 1/6 (16.7%), or 96 h in 1/6 (16.7%) patients after cessation of seizures. Repeat MRI revealed disappearance of signal changes in two patients. Peri-ictal MR changes with restricted diffusion appear to be an effect rather than the cause of SE. (orig.)

  14. Protective effects of endoplasmic reticulum stress preconditioning on hippocampal neurons in rats with status epilepticus

    Yi ZHANG

    2014-12-01

    Full Text Available Objective To evaluate the protective effects of endoplasmic reticulum stress preconditioning induced by 2-deoxyglucose (2-DG on hippocampal neurons of rats with status epilepticus (SE and the possible mechanism.  Methods Ninety Sprague-Dawley (SD rats were randomly enrolled into preconditioning group (N = 30, SE group (N = 30 and control group (N = 30. Each group was divided into 6 subsets (N = 5 according to six time points (before seizure, 6 h, 12 h, 1 d, 2 d and 7 d after seizure. The preconditioning group was administered 2-DG intraperitoneally with a dose of 150 mg/kg for 7 days, and the lithium-pilocarpine induced SE rat model was established on both preconditioning group and SE group. The rats were sacrificed at the above six time points, and the brains were removed to make paraffin sections. Nissl staining was performed by toluidine blue to evaluate the hippocampal neuronal damage after seizure, and the number of survival neurons in hippocampal CA1 and CA3 regions of the rats were counted. Immunohistochemical staining was performed to detect the expressions of glucose regulated protein 78 (GRP78 and X-box binding protein 1 (XBP-1 in hippocampal CA3 region of the rats.  Results The number of survival neurons in preconditioning group was much more than that in SE group at 7 d after seizure (t = 5.353, P = 0.000, and was more obvious in CA1 region. There was no significant hippocampal neuronal damage in control group. The expressions of GRP78 and XBP-1 in CA3 region of hippocampus in SE group at 6 h after seizure were significantly higher than that in control group (P = 0.000, and then kept increasing until reaching the peak at 2 d (P = 0.000, for all. The expressions of GRP78 and XBP-1 in hippocampal CA3 region in preconditioning group were significantly higher than that in control group before seizure (P = 0.000, for all. The level of GRP78 maintained the highest at 24 h and 2 d after seizure (P = 0.000, for all, while the XBP-1 level

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

    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

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

    Dhote, Franck, E-mail: franck.dhote@irba.fr [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Carpentier, Pierre; Barbier, Laure [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Peinnequin, André [Département Effets biologiques des rayonnements, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Baille, Valérie; Pernot, Fabien; Testylier, Guy; Beaup, Claire; Foquin, Annie [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); 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

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

    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

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

    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

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

    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

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

    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

  1. The effect of STAT3 Inhibition on status epilepticus and subsequent spontaneous seizures in the Pilocarpine Model of Acquired Epilepsy

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

    2013-01-01

    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 effects 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-EE...

  2. Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization: current clinical status

    Marcus, Stuart L.; Golub, Allyn L.; Shulman, D. Geoffrey

    1995-03-01

    Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization (ALA PDT) via endogenous protoporphyrin IX (PpIX) synthesis has been reported as efficacious, using topical formulations, in the treatment of a variety of dermatologic diseases including superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses. Application of ALA PDT to the detection and treatment of both malignant and non-malignant diseases of internal organs has recently been reported. Local internal application of ALA has been used for the detection, via PpIX fluorescence, of pathological conditions of the human urinary bladder and for selective endometrial ablation in animal model systems. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer and of colorectal cancer. This paper reviews the current clinical status of ALA PDT.

  3. Continuous infusion of midazolam in the treatment of refractory generalized convulsive status epilepticus.

    Ulvi, H; Yoldas, T; Müngen, B; Yigiter, R

    2002-10-01

    We studied the efficacy and safety of midazolam given as a continuous infusion in the treatment of refractory generalized convulsive status epilepticus (RGCSE). We carried out a prospective, open study, in 19 patients (11 men) with RGCSE in the intensive care unit at Firat Medical Center in Elazig. When intravenous administration of 0.3 mg/kg diazepam (three times at 5-min intervals), 20 mg/kg phenytoin, and 20 mg/kg phenobarbital failed to bring the episode under control, patients were administered an intravenous bolus of midazolam (200 microg/kg) followed by a continuous infusion at 1 microg/kg min. The dose was increased by 1 microg/kg min every 15 min until the episode of seizure was brought under control. The time from beginning of treatment to control of seizures, infusion rate, and side-effects were monitored. The mean age of the patients was 40.4 years (range 16-87 years). The clinical etiology of RGCSE was idiopathic epilepsy (6 cases), anoxicischemic cerebral insult due to cardiac arrest (3), viral encephalitis (2), intrahemispheric hematoma due to hemorrhagic stroke (1), cerebral infarct due to ischemic stroke (1), pituitary adenoma (1), post-traumatic epilepsy (1), renal failure (1), tuberculous meningitis (1), and unknown (2). In eighteen (94.7%) patients, seizures were completely controlled in a mean time of 45 min (range, 5-120 min) at a mean infusion rate of 8 microg/kg min (range, 3-21 microg/kg min). In one patient seizures did not stop. Midazolam administration did not cause any significant change in blood pressure, heart rate, oxygen saturation, or respiratory status. The mean time to full consciousness for patients after stopping the infusion was 1.6 hours (range, 2.0-8.5 hours). The mean infusion duration of midazolam was 14.5 hours (range, 12-25 hours). Midazolam is an effective and safe drug to control RGCSE, and may represent a substantial improvement over current therapeutic approaches such as pentobarbital anesthesia. PMID:12536286

  4. Region-specific vulnerability to endoplasmic reticulum stress-induced neuronal death in rat brain after status epilepticus

    Jing Chen; Hu Guo; Guo Zheng; Zhong-Nan Shi

    2013-12-01

    We sought to clarify the involvement and the intra-cerebral distribution variability of C/EBP homologous protein (CHOP), a representative molecule related to endoplasmic reticulum (ER) stress-induced cell death signalling pathways, in neuronal death resulting from status epilepticus in rats. The expression patterns of CHOP and glucose-regulated protein (GRP) 78, a good marker of ER stress, were assessed by Western blotting, real-time PCR, Hoechst and immunohistochemistry in the hippocampus, cortex and striatum on a status epilepticus (SE) model. Double-fluorescent staining of CHOP and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labelling (TUNEL) method were performed to clarify the involvement of CHOP in cell death. SE resulted in a time-dependent increase in the expression of GRP78 and CHOP. The expression of GRP78 protein was increased at 3, 6 and 12 h after SE and no brain region variability was found. The expression of CHOP protein was also increased, reached its peak at 24 h and remained high at 48 h. CHOP protein expression, however, showed brain region variability with highest expression noted in the hippocampus followed by the striatum, and lowest in the cortex. The up-regulation of CHOP occurring at the transcriptional level was demonstrated by real-time PCR. Double fluorescence showed that CHOP expression strongly correlated with neurons undergoing apoptosis. The results indicated that SE compromises the function of the ER and that the hippocampus is more vulnerable than the cortex and the striatum.

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

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

    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

  7. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  8. LiCl/Pilocarpine - induced status epilepticus and ischemic hippocampal lesion induced by endothelin-1:two models of epileptogenesis in immature rats

    Kubová, Hana

    Sitges: -, 2008. s. 89-89. [Eilat conference on new antiepileptic drugs /9./. 15.06.2008-19.06.2008, Sitges] Institutional research plan: CEZ:AV0Z50110509 Keywords : spo2 * status epilepticus * ischemic lesion * immature rats Subject RIV: FH - Neurology

  9. Efficacy and safety of non-intravenous midazolam for the treatment of status epilepticus in children: a Meta-analysis

    Yan LIN

    2016-02-01

    Full Text Available Objective To evaluate the clinical efficacy and safety of non-intravenous midazolam for treating status epilepticus (SE in children.  Methods Taking midazolam, status epilepticus and children both in Chinese and English as search terms, retrieve in databases such as PubMed, ScienceDirect, China National Knowledge Infrastructure (CNKI, VIP and Wanfang Data, assisted by manual searching and Google Scholar, in order to collect randomized controlled trials (RCTs about non-intravenous midazolam for treating SE in children from January 2000 to January 2015. Jadad Scale was used to evaluate the quality of literatures. Meta-analysis was performed by using RevMan 5.3 software. Results There were a total of 258 records after preliminary searching, and 6 RCTs involving 766 episodes were finally included after excluding duplicate ones and those which did not meet the inclusion criteria. The results were as follows: 1 midazolam via intranasal administration was as effective as intravenous diazepam in achieving seizure control in children (RD = -0.070, 95%CI: -0.200—0.060, P = 0.290. However, non-intravenous (intranasal or buccal midazolam showed better effects on seizure control than rectal diazepam (RD = 0.170, 95% CI: 0.030—0.320; P = 0.020. 2 The mean time from arrival at hospital to cessation was not significantly different between intranasal midazolam and intravenous diazepam (SMD = -1.570, 95%CI: -3.280—0.140; P = 0.070. 3 There was no statistical difference between intranasal midazolam and intravenous diazepam for the time from giving drug to cessation (SMD = 0.240, 95%CI: -0.110—0.590; P = 0.170. 4 There was no statistical difference on the occurrence rate of adverse drug reactions between non-intravenous midazolam and intravenous or non-intravenous diazepam (RD = -0.010, 95% CI: -0.030—0.200; P = 0.500.  Conclusions Non-intravenous midazolam is safe and effective in the treatment for status epilepticus in children. However, the

  10. COMPARATIVE EFFECTS OF DIAZEPAM INFUSION AND DIVIDED DOSES OF DIAZEPAM ON THE TREATMENT OF ABSENCE STATUS EPILEPTICUS

    L. Afshar khas

    2009-06-01

    Full Text Available ObjectiveAbsence status epilepticus (ASE is a common form of nonconvulsive status epilepcticus. It is characterized by loss of consciousness with spike and wave discharges in EEG simultaneously. The most effective treatment of ASE is diazepam, either infusion or in divided doses; the former is more expensive since patients must be admitted in an Intensive Care Unit. The aim of this study was to evaluate and compare the efficacy of diazepam infusion and parenteral diazepam in divided doses in the treatment of ASE.Materials & MethodsThis randomized controlled clinical trial, enrolled 20 patients with absence status epilepticus. Diagnosis was made based on the clinical manifestations and electroencephalogram (EEG. Prior to treatment, all patients underwent EEG and imaging. Patients were randomized to receive 0.2 mg/kg/h diazepam infusion or 0.2 mg/kg in six daily doses. Clinical and EEG improvements were considered to be optimal responses.ResultsOf the 20 patients studied, 13 (65% were boys and the remaining 7(35% were girls. There were no differences between the two groups regarding age and sex (non-significant. Following treatments after 48 hours, 1 week and 1 month respectively, clinical improvement in previous problems (loss of consciousness, ataxia, behavior and speech problems and EEGs was similar in both groups (p=1. There were controlled seizures in 18 (90%, abnormal CT scans in 5 (25%, abnormal EEGs after treatments in 6 (30% cases; however no significant differences were seen between the two groups.ConclusionThis study demonstrates that there are no significant differences between treatments of ASE with diazepam infusion and parenteral diazepam in divided doses. Treatment of ASE, with divided doses of diazepam is easier, less expensive and patients do not require to be hospitalized in an Intensive Care unit.

  11. 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

    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

  12. Effects of LiCl/pilocarpine-induced status epilepticus on rat brain mu and benzodiazepine receptor binding: Regional and ontogenetic studies

    Rocha, L.; Suchomelová, Lucie; Mareš, Pavel; Kubová, Hana

    2007-01-01

    Roč. 1181, - (2007), s. 104-117. ISSN 0006-8993 R&D Projects: GA MŠk(CZ) LC554; GA ČR GA304/05/2582 Grant ostatní: CONACyT(MX) 45943-M Institutional research plan: CEZ:AV0Z50110509 Keywords : benzodiazepine receptor * µ receptor binding * status epilepticus Subject RIV: ED - Physiology Impact factor: 2.218, year: 2007

  13. Evaluation of the efficacy of sodium valproate in convulsive status epilepticus following to ıschemic stroke

    Hasan Hüseyin Özdemir

    2015-04-01

    Full Text Available Objective : Convulsive status epilepticus (CSE is very rarely observed after ischaemic stroke. Sodium valproate (SV is one of the agents used in the treatment of CSE, but its role still controversial, and its degree of efficacy in treating CSE that develops following stroke is unclear. Method : We evaluated 19 patients who were treated with intravenous (IV SV (20 mg/kg, 2 mg/kg/h-12h after diazepam. Patients’ modified Rankin scores (mRS, SE types, and changes in biochemical parameters after treatment were assessed. Results : CSE was successfully treated in 12 (63.15% patients. Side effects such as hypotension and allergic reactions were observed in two patients. Refractory SE development was observed in 5 (29.4% patients with high mRS (˃ 3. No significant deterioration in patients’ laboratory evaluations, conducted before and after status, was observed. Conclusion : SV may be safe and effective in the treatment of CSE observed after ischaemic stroke, especially in patients with low mRS.

  14. Níveis dos neurotransmissores estriatais durante o estado epiléptico Striatal monoamines levels during status epilepticus

    Rivelilson Mendes de Freitas

    2003-01-01

    Full Text Available O objetivo desse estudo foi verificar os níveis dos neurotransmissores estriatais de ratas adultas durante o estado epiléptico induzido pela pilocarpina. Ratas wistar foram tratadas com uma única dose de pilocarpina (400 mg/kg por via subcutânea (S.C.; P400 e os controles receberam salina. A concentração dos neurotransmissores foi determinada através do HPLC eletroquímico, no corpo estriado de ratas que no período de observação de 1 hora desencadearam estado epiléptico e que sobreviveram à fase aguda do quadro convulsivo. Foi observada redução nos níveis de dopamina, serotonina, ácido diidroxifenilacético e aumento na concentração do ácido 5-hidroxiindolacético. Nenhuma alteração foi observada no 4-hidroxi-3-metoxi-fenilacético. Os resultados sugerem que a ativação do sistema colinérgico pode interagir com os sistemas dopaminérgico e serotonérgico nos mecanismos referentes à fase aguda do processo convulsivo no corpo estriado de ratos desenvolvidos.The purpose of the present work to investigate the striatal neurotransmissors level in adult rats after status epilepticus induced by pilocarpine. Wistar rats were treated with a single dose of pilocarpine (400 mg/kg; s.c.; P400 and the controls received saline. Adult animals were closed observed for behavioural changes during 1h. In this period, the animals that developed status epilepticus and survive this acute phase of seizures had the brains removed and striatal neurotransmissors level determiden by HPLC. The concentration of dopamine, serotonine, dihydroxyphenylacetic acid was reduced and an concentration increase in 5-hydroxyindolacetic acid. Didn't observed alteration in 4-hydroxy-3-methoxy-phenylacetic acid. These results suggest that cholinergic activation can interage with dopaminergic and serotonergic systems in acute phase of the convulsive process in rat mature striatum.

  15. Reduced expression of calsenilin/DREAM/KChIP3 in the brains of kainic acid-induced seizure and epilepsy patients.

    Hong, Yeon-Mi; Jo, Dong-Gyu; Lee, Min-Cheol; Kim, So-Young; Jung, Yong-Keun

    2003-04-01

    Calsenilin is a neuronal calcium binding protein that may function in calcium signaling and cell death. Kainic acid, an analog of the excitatory amino acid L-glutamate, produced excitotoxic cell death and induced the pathophysiology of status epilepticus. The expression of calsenilin was investigated in the mouse brain after kainic acid-induced seizure and seizure-induced hippocampal neuronal cell culture system using immunostaining analysis. Calsenilin was markedly decreased not only in the damaged cortex and CA3 region of hippocampus at 24 h after kainic acid-induced seizure but also in a cell-culture model of seizure-like activity. In addition, immunoreactivity of calsenilin in the hippocampus derived from human epilepsy patient was significantly decreased compared with normal brain. These results demonstrate that the reduced expression of calsenilin may functionally be associated with the pathophysiology of status epilepticus. PMID:12648752

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

    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

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

    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. Histamine 1 receptor knock out mice show age-dependent susceptibility to status epilepticus and consequent neuronal damage.

    Kukko-Lukjanov, Tiina-Kaisa; Grönman, Maria; Lintunen, Minnamaija; Laurén, Hanna B; Michelsen, Kimmo A; Panula, Pertti; Holopainen, Irma E

    2012-06-01

    The central histaminergic neuron system is an important regulator of activity stages such as arousal and sleep. In several epilepsy models, histamine has been shown to modulate epileptic activity and histamine 1 (H1) receptors seem to play a key role in this process. However, little is known about the H1 receptor-mediated seizure regulation during the early postnatal development, and therefore we examined differences in severity of kainic acid (KA)-induced status epilepticus (SE) and consequent neuronal damage in H1 receptor knock out (KO) and wild type (WT) mice at postnatal days 14, 21, and 60 (P14, P21, and P60). Our results show that in P14 H1 receptor KO mice, SE severity and neuronal damage were comparable to those of WT mice, whereas P21 KO mice had significantly decreased survival, more severe seizures, and enhanced neuronal damage in various brain regions, which were observed only in males. In P60 mice, SE severity did not differ between the genotypes, but in KO group, neuronal damage was significantly increased. Our results suggest that H1 receptors could contribute to regulation of seizures and neuronal damage age-dependently thus making the histaminergic system as a challenging target for novel drug design in epilepsy. PMID:22348791

  19. P2X7 receptor-mediated PARP1 activity regulates astroglial death in the rat hippocampus following status epilepticus

    Ji Yang eKim

    2015-09-01

    Full Text Available Poly(ADP-ribose polymerase-1 (PARP1 plays a regulatory role in apoptosis, necrosis, and other cellular processes after injury. Recently, we revealed that PARP1 regulates the differential neuronal/astroglial responses to pilocarpine-induced status epilepticus (SE in the distinct brain regions. In addition, P2X7 receptor (P2X7R, an ATP-gated ion channel, activation accelerates astroglial apoptosis, while it attenuates clasmatodendrosis (lysosome-derived autophagic astroglial death. Therefore, we investigated whether P2X7R regulates regional specific astroglial PARP1 expression/activation in response to SE. In the present study, P2X7R activation exacerbates SE-induced astroglial apoptosis, while P2X7R inhibition attenuates it accompanied by increasing PARP1 activity in the molecular layer of the dentate gyrus following SE. In the CA1 region, however, P2X7R inhibition deteriorates SE-induced clasmatodendrosis via PARP1 activation following SE. Taken together, our findings suggest that P2X7R function may affect SE-induced astroglial death by regulating PARP1 activation/expression in regional-specific manner. Therefore, the selective modulation of P2X7R-mediated PARP1 functions may be a considerable strategy for controls in various types of cell deaths.

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

    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

  1. Assessment of effect of ethanolic extract of Tephrosia purpurea (L. Pers., Fabaceae, activity on lithium-pilocarpine induced Status epilepticus and oxidative stress in Wistar rats Avaliação do efeito do extrato etanólico da Tephrosia purpurea (L. Pers., Fabaceae, sobre o status epilepticus induzido por lítio-pilocarpina e estresse oxidativo, em ratos Wistar

    G Asuntha

    2010-11-01

    Full Text Available Tephrosia purpurea (L. Pers., Fabaceae, is claimed to be of use in the control and treatment of a variety of epileptic disorders in Indian system of medicine. The present study plans to systematically evaluate T. purpurea and to verify this claim. Status epilepticus was induced in male albino rats of Wistar strain by administration of pilocarpine (30 mg/kg, i.p. 24 h after lithium chloride (3 mEq/kg, i.p.. Different doses of the extract of T. purpurea were administered orally one hour before the injection of pilocarpine. The severity of status epilepticus was observed and recorded every 15 min till 90 min and thereafter every 30 min till 180 min, using the scoring system. The in vivo lipid peroxidation of rat brain tissue was measured. The in vitro NO free radical scavenging activity of plant extract was assessed. The interaction between plant extract and 2-diphenyl-2-picryl hydrazyl (DPPH was also observed for in vitro free radical scavenging activity. The severity of status epilepticus was reduced with the administration of ethanolic extract of T. purpurea. Ethanolic extract of the plant exhibited both in vivo and in vitro antioxidant activity. The ethanolic extract of T. purpurea was found to be useful to control lithium-pilocarpine induced status epilepticus in albino rats of Wistar strain.Tephrosia purpurea (L. Pers., Fabaceae, é conhecida pelo seu uso no controle e tratamento de uma variedade de distúrbios epilépticos no sistema indiano de medicina. O presente estudo pretende avaliar de forma sistemática T. purpurea e verificar essa alegação. Status epilepticus foi induzido em ratos albinos machos da linhagem Wistar pela administração de pilocarpina (30 mg/kg, i.p. 24 h após o cloreto de lítio (3 mEq/kg, i.p.. Diferentes doses do extrato de T. purpurea foram administrados por via oral uma hora antes da injeção de pilocarpina. A gravidade do status epilepticus foi observada e registrada a cada 15 min até 90 min e

  2. Status epilepticus after prolonged umbilical cord occlusion is associated with greater neural injury in [corrected] fetal sheep at term-equivalent.

    Paul P Drury

    Full Text Available The majority of pre-clinical studies of hypoxic-ischemic encephalopathy at term-equivalent have focused on either relatively mild insults, or on functional paradigms of cerebral ischemia or hypoxia-ischemia/hypotension. There is surprisingly little information on the responses to single, severe 'physiological' insults. In this study we examined the evolution and pattern of neural injury after prolonged umbilical cord occlusion (UCO. 36 chronically instrumented fetal sheep at 125-129 days gestational age (term = 147 days were subjected to either UCO until mean arterial pressure was < = 8 mmHg (n = 29, or sham occlusion (n = 7. Surviving fetuses were killed after 72 hours for histopathologic assessment with acid-fuchsin thionine. After UCO, 11 fetuses died with intractable hypotension and 5 ewes entered labor and were euthanized. The remaining 13 fetuses showed marked EEG suppression followed by evolving seizures starting at 5.8 (6.8 hours (median (interquartile range. 6 of 13 developed status epilepticus, which was associated with a transient secondary increase in cortical impedance (a measure of cytotoxic edema, p<0.05. All fetuses showed moderate to severe neuronal loss in the hippocampus and the basal ganglia but mild cortical cell loss (p<0.05 vs sham occlusion. Status epilepticus was associated with more severe terminal hypotension (p<0.05 and subsequently, greater neuronal loss (p<0.05. In conclusion, profound UCO in term-equivalent fetal sheep was associated with delayed seizures, secondary cytotoxic edema, and subcortical injury, consistent with the predominant pattern after peripartum sentinel events at term. It is unclear whether status epilepticus exacerbated cortical injury or was simply a reflection of a longer duration of asphyxia.

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

    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

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

    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

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

    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 (pclass 5 seizures repeated themselves more times (pclasses 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

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

    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

  7. Experience in using injectable valproic acid (convulex in patients with serial epileptic seizures and status epilepticus at the prehospital stage

    A. V. Lebedeva

    2014-01-01

    Full Text Available Objective: to evaluate the efficacy of injectable valproate (convulex in patients with serial epileptic seizures and status epilepticus (SE at the prehospital stage.Patients and methods. Thirty-two adult patients, including 17 (53% men and 15 (47% women, were examined. Most patients were aged over 40 years (mean age 54.7±9.4 years. To define the required dose of the drug, the authors estimated the patient's weight that averaged 76.8±1.9 kg, i.e. there was a preponderance of patients who needed convulex, more than 500 mg, to achieve a therapeutic effect.Results. It was impossible to reliably and validly evaluate the type of a seizure as the medical emergency team (MET generally observed the patient with a just evolving seizure and the medical history data were not always valid therefore the type of convulsions and the type of a seizure were evaluated. In most cases, solitary convulsive attacks (tonic and/or clonic convulsions and/or serial seizures were observed in 12 (37.5% and 14 (43.7% patients, respectively; SE was recorded in 6 (8.8% patients. Generalized seizures (without a clear focal onset were prevalent in 24 (75% patients while 8 (25% patients were found to have partial seizures (seizure onset lateralization, a focal onset. According to the pattern of convulsions, seizures may be classified into three types: tonic-clonic, clonic, and tonic in 22 (68.8%, 7 (21.9%, and 3 (9.3% patients, respectively. Analysis of the efficacy of intravenously injectable valproate (convulex in the group of patients with SE and epileptic seizures indicated that complete cessation of seizures could be achieved in 68.8%, their rate decreased in other 9.4% of the patients. Seizures were preserved in 7 (21.8% cases, which required additional administration of drugs. Conclusion. Injectable valproic acid (convulex has a high efficacy and may be preclinically used as the drug of choice to arrest SE and serial seizures caused by both epilepsy and other

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

    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

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

    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

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

    Abdulaziz Salman

    2012-12-01

    Full Text Available Abstract 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.

  11. Alterative application of five anticonvulsants according to the half life for the treatment of status epilepticus in children with severe viral encephalitis

    2007-01-01

    BACKGROUND: Traditional subhibernation therapy may easily cause complications, such as respiratory depression and hyportension because of application of chlorpromazine hydrochloride and promethazine in a large dosage.OBJECTIVE: To observe therapeutic effect of modified subhibernation therapy (alterative application of five anticonvulsants according to the half life) on status epilepticus in children with severe viral encephalitis (VE).DESIGN: Contrast observation.SETTING: Department of Pediatrics, the First Hospital of Jilin University.PARTICIPANTS: The participants in present study were 96 patients withsevere viral encephalitis including 52 boys and 44 girls who received treatment in the Department of Pediatrics, the First Hospital of Jilin University from February 2000 to March 2006. All children met the diagnostic criteria of Zhufutong Practice Pediatrics (the seventh edition). Two weeks ago, they ever got upper respiratory infection or enteronitis and so on before the onset, spirit abnormal, behavior disorder, limbs act disorder, vomit, headache, convulsion,nervous system masculine signs such as limbs act disord, autonomic nerve damage manifestation, brain nerve palsy, dysreflexia, meningeal irritation sign, cerebrospinal fluid and electroencephalography (EEG)abnormity. All parents provided the confirmed consent. The patients were randomly divided into control group (n =40) and experimental group (n =56).METHODS: Patients in the control group received anticonvulsion, ice compress and routine treatment. The convulsion was treated with five drugs: 0.5 mg/kg wintermin and phenergan, respectively, 100 g/L chlorpromazine hydrochloride (0.5 mL/kg), 5 mg/kg luminal, 0.3 mg/kg ansiolin. When convulsion attacked,those five drugs were given alternatively; however, those were not given if the convulsion did not attack.Children in the experimental group were treated with improved subhibernation therapy based on routine treatment. The dosages of anticonvulsants were as the

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

    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

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

    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

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

    Mohammad Ahmad

    2014-01-01

    Full Text Available 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.

  15. [Abnormal cerebral blood flow distributions during the post-ictal phase of febrile status epilepticus in three pediatric patients measured by arterial spin labeling perfusion MRI].

    Hirano, Keiko; Fukuda, Tokiko

    2016-05-01

    The ability to visualize brain perfusion is important for identifying epileptic foci. We present three pediatric cases showing asymmetrical cerebral blood flow (CBF) distributions during the post-ictal phase of febrile status epilepticus measured by arterial spin labeling (ASL) perfusion MRI. During the acute phase, regional CBF measurements in the areas considered including epileptic foci were higher than in the corresponding area of the contralateral hemisphere, though the exact quantitative value varied between cases. We could not identify the correct epileptogenic foci, because those ASL images were taken after the prolonged and extraordinary activation of neurons in the affected area. During the recovery phase, the differences reduced and the average regional CBF measurement was 54.6 ± 6.1 ml/100 g per minute, which was a little less than the number of previous ASL studies. ASL perfusion MRI imaging provides a method for evaluating regional CBF by using magnetically labeled arterial blood water as an endogenous tracer. With this technique, we can repeatedly evaluate both the brain structure and the level of perfusion at the same time. ASL is noninvasive and easily accessible, and therefore it could become a routine tool for assessment of perfusion in daily practice of pediatric neurology. PMID:27349086

  16. Neuroprotective effect of therapeutic hypothermia versus standard care alone after convulsive status epilepticus: protocol of the multicentre randomised controlled trial HYBERNATUS.

    Legriel, Stephane; Pico, Fernando; Tran-Dinh, Yves-Roger; Lemiale, Virginie; Bedos, Jean-Pierre; Resche-Rigon, Matthieu; Cariou, Alain

    2016-12-01

    Convulsive status epilepticus (CSE) is a major medical emergency associated with a 50 % morbidity rate. CSE guidelines have recommended prompt management for many years, but there is no evidence to date that they have significantly improved practices or outcomes. Developing neuroprotective strategies for use after CSE holds promise for diminishing morbidity and mortality rates. Hypothermia has been shown to afford neuroprotection in various health conditions. We therefore designed a trial to determine whether 90-day outcomes in mechanically ventilated patients with CSE requiring management in the intensive care unit (ICU) are improved by early therapeutic hypothermia (32-34 °C) for 24 h with propofol sedation. We are conducting a multicentre, open-label, parallel-group, randomised, controlled trial (HYBERNATUS) of potential neuroprotective effects of therapeutic hypothermia and routine propofol sedation started within 8 h after CSE onset in ICU patients requiring mechanical ventilation. Included patients are allocated to receive therapeutic hypothermia (32-34 °C) plus standard care or standard care alone. We plan to enrol 270 patients in 11 ICUs. An interim analysis is scheduled after the inclusion of 135 patients. The main study objective is to evaluate the effectiveness of therapeutic hypothermia (32-34 °C) for 24 h in diminishing 90-day morbidity and mortality (defined as a Glasgow Outcome Scale score <5). The HYBERNATUS trial is expected to a decreased proportion of patients with a Glasgow Outcome Scale score lower than 5 after CSE requiring ICU admission and mechanical ventilation. Trial registration Clinicaltrials.gov identifier NCT01359332 (registered on 23 May 2011). PMID:27325409

  17. Immediate Epileptogenesis after Kainate-Induced Status Epilepticus in C57BL/6J Mice: Evidence from Long Term Continuous Video-EEG Telemetry.

    Sreekanth Puttachary

    Full Text Available The C57BL/6J mouse as a model of seizure/epilepsy is challenging due to high mortality and huge variability in response to kainate. We have recently demonstrated that repeated administration of a low dose of kainate by intraperitoneal route can induce severe status epilepticus (SE with 94% survival rate. In the present study, based on continuous video-EEG recording for 4-18 weeks from epidurally implanted electrodes on the cortex, we demonstrate that this method also induces immediate epileptogenesis (<1-5 days post-SE. This finding was based on identification of two types of spontaneous recurrent seizures; behavioral convulsive seizures (CS and electrographic nonconvulsive seizures (NCS. The identification of the spontaneous CS, stage 3-5 types, was based on the behaviors (video that were associated with the EEG characteristics (stage 3-5 epileptiform spikes, the power spectrum, and the activity counts. The electrographic NCS identification was based on the stage 1-2 epileptiform spike clusters on the EEG and their associated power spectrum. Severe SE induced immediate epileptogenesis in all the mice. The maximum numbers of spontaneous CS were observed during the first 4-6 weeks of the SE and they decreased thereafter. Mild SE also induced immediate epileptogenesis in some mice but the CS were less frequent. In both the severe and the mild SE groups, the spontaneous electrographic NCS persisted throughout the 18 weeks observation period, and therefore this could serve as a chronic model for complex seizures. However, unlike rat kainate models, the C57BL/6J mouse kainate model is a unique regressive CS model of epilepsy. Further studies are required to understand the mechanism of recovery from spontaneous CS in this model, which could reveal novel therapeutic targets for epilepsy.

  18. Benign childhood epilepsy with Centro-Temporal spikes (BCECTSs), electrical status epilepticus in sleep (ESES), and academic decline--how aggressive should we be?

    Uliel-Sibony, Shimrit; Kramer, Uri

    2015-03-01

    Since many of the children with BCECTSs display electrical status epilepticus during sleep and many present with different comorbidities, mainly ADHD and behavioral disturbances, clinicians are often confronted with the dilemma of how aggressive they should be with their efforts of normalizing the EEG. We conducted a retrospective study by screening medical records of all consecutive patients with BCECTSs, spike-wave index (SWI) >30%, and ADHD/ADD that were evaluated in our pediatric epilepsy service and were followed up for at least two years. Patients with neurocognitive deterioration detected by formal testing were excluded. A total of 17 patients with mean age of 6.9years at BCECTS diagnosis were identified. The patients' mean SWI was 60% and that dense electrical activity lasted 1.5years on average (range: 1-4.5years). Six children were formally diagnosed with learning disabilities in addition to ADD/ADHD. All of them were treated with an average of three antiepileptic medications, mainly for the purpose of normalizing the EEG, but none of them was treated with steroids or high-dose diazepam. The mean duration of follow-up was 5.5years. A cognitive or behavioral deterioration was not detected in any of them. Our data suggest that when treating a child with BCECTSs, high SWI, and school difficulties, the most critical parameter that determines the necessity of using second-line antiepileptic agents such as steroids or high-dose diazepam is a formal psychological evaluation that proves cognitive (I.Q.) decline. Otherwise, these agents may be avoided. PMID:25678032

  19. Temporal profiles of age-dependent changes in cytokine mRNA expression and glial cell activation after status epilepticus in postnatal rat hippocampus

    Ruohonen Saku

    2011-04-01

    Full Text Available Abstract Background Status epilepticus (SE is proposed to lead to an age-dependent acute activation of a repertoire of inflammatory processes, which may contribute to neuronal damage in the hippocampus. The extent and temporal profiles of activation of these processes are well known in the adult brain, but less so in the developing brain. We have now further elucidated to what extent inflammation is activated by SE by investigating the acute expression of several cytokines and subacute glial reactivity in the postnatal rat hippocampus. Methods SE was induced by an intraperitoneal (i.p. injection of kainic acid (KA in 9- and 21-day-old (P9 and P21 rats. The mRNA expression of interleukin-1 beta (IL-1β, tumor necrosis factor-alpha (TNF-α, interleukin-10 (IL-10, matrix metalloproteinase-9 (MMP-9, glial-derived neurotrophic factor (GDNF, interferon gamma (IFN-γ, and transforming growth factor-beta 1 (TGF-β1 were measured from 4 h up to 3 days after KA injection with real-time quantitative PCR (qPCR. IL-1β protein expression was studied with ELISA, GFAP expression with western blotting, and microglial and astrocyte morphology with immunohistochemistry 3 days after SE. Results SE increased mRNA expression of IL-1β, TNF-α and IL-10 mRNA in hippocampus of both P9 and P21 rats, their induction being more rapid and pronounced in P21 than in P9 rats. MMP-9 expression was augmented similarly in both age groups and GDNF expression augmented only in P21 rats, whereas neither IFN-γ nor TGF-β1 expression was induced in either age group. Microglia and astrocytes exhibited activated morphology in the hippocampus of P21 rats, but not in P9 rats 3 d after SE. Microglial activation was most pronounced in the CA1 region and also detected in the basomedial amygdala. Conclusion Our results suggest that SE provokes an age-specific cytokine expression in the acute phase, and age-specific glial cell activation in the subacute phase as verified now in the

  20. Lovastatin reduces neuronal cell death in hippocampal CA1 subfield after pilocarpine-induced status epilepticus: preliminary results Lovastatina reduz a lesão celular na região CA1 do hipocampo após o status epilepticus induzido pela pilocarpina: resultados preliminares

    Pauline Rangel

    2005-12-01

    Full Text Available OBJECTIVE: To further characterize the capacity of lovastatin to prevent hippocampal neuronal loss after pilocarpine-induced status epilepticus (SE METHOD: Adult male Wistar rats were divided into four groups: (A control rats, received neither pilocarpine nor lovastatin (n=5; (B control rats, received just lovastatin (n=5; (C rats that received just pilocarpine (n=5; (D rats that received pilocarpine and lovastatin (n=5. After pilocarpine injection (350mg/kg, i.p., only rats that displayed continuous, convulsive seizure activity were included in our study. Seizure activity was monitored behaviorally and terminated with an injection of diazepam (10 mg/kg, i.p. after 4 h of convulsive SE. The rats treated with lovastatin received two doses of 20mg/kg via an oesophagic probe immediately and 24 hours after SE induction. Seven days after pilocarpine-induced SE, all the animals were perfused and their brains were processed for histological analysis through Nissl method. RESULTS: The cell counts in the Nissl-stained sections performed within the hippocampal formation showed a significant cell loss in rats that received pilocarpine and presented SE (CA1= 26.8 ± 13.67; CA3= 38.1 ± 7.2; hilus= 43.8 ± 3.95 when compared with control group animals (Group A: CA1= 53.2 ± 9.63; CA3= 63.5 ± 13.35; hilus= 59.08 ± 10.24; Group B: CA1= 74.3 ± 8.16; CA3= 70.1 ± 3.83; hilus= 70.6 ± 5.10. The average neuronal cell number of CA1 subfield of rats that present SE and received lovastatin (44.4 ± 17.88 was statically significant increased when compared with animals that just presented SE. CONCLUSION: Lovastatin exert a neuroprotective role in the attenuation of brain damage after SE.OBJETIVO: Capacidade da lovastatina em prevenir a perda de neurônios hipocampais após o status epilepticus (SE induzido pela pilocarpina. MÉTODO: Ratos adultos Wistar foram divididos em 4 grupos: (A ratos controles que não receberam pilocarpina nem lovastatina (n=5; (B ratos

  1. A New Derivative of Valproic Acid Amide Possesses a Broad-spectrum Antiseizure Profile and Unique Activity Against Status Epilepticus and Organophosphate Neuronal Damage

    White, H. Steve; Alex, Anitha B.; Pollock, Amanda; Hen, Naama; Shekh-Ahmad, Tawfeeq; Wilcox, Karen S.; McDonough, John H.; Stables, James P.; Kaufmann, Dan; Yagen, Boris; Bialer, Meir

    2011-01-01

    Summary Purpose sec-Butyl-propylacetamide (SPD) is a one-carbon homologue of valnoctamide (VCD), a CNS-active amide derivative of valproic acid (VPA) currently in phase II clinical trials. The current study evaluated the anticonvulsant activity of SPD in a battery of rodent seizure and epilepsy models and assessed its efficacy in rat and guinea pig models of status epilepticus (SE) and neuroprotection in an organotypic hippocampal slice model of excitotoxic cell death. Methods SPD’s anticonvulsant activity was evaluated in several rodent seizure and epilepsy models including: maximal electroshock (MES), 6Hz psychomotor, subcutaneous (s.c.) metrazol-, s.c., picrotoxin, s.c. bicuculline, audiogenic and corneal and hippocampal kindled seizures following intraperitoneal administration. Results obtained with SPD are discussed in relationship to those obtained with VPA and VCD. SPD was also evaluated for its ability to block benzodiazepine-resistant SE induced by pilocarpine (rats) and soman (rats and guinea pigs) following intraperitoneal administration. SPD was tested for its ability to block excitotoxic cell death induced by the glutamate agonists N-methyl-D-Aspartate (NMDA) and kainic acid (KA) using organotypic hippocampal slices and SE-induced hippocampal cell death using FluoroJade B staining. The cognitive function of SPD-treated rats that were protected against pilocarpine-induced convulsive SE was examined 10-14 days post SE using the Morris water maze (MWM). The relationship between the pharmacokinetic profile of SPD and its efficacy against soman-induced SE was evaluated in two parallel studies following SPD (60 mg/kg, i.p.) administration in the soman SE rat model. Key Findings SPD was highly effective and displayed a wide protective index (PI=TD50/ED50) in the standardized seizure and epilepsy models employed. SPD’s wide PI values demonstrate that it is effective at doses well below those that produce behavioral impairment. Unlike VCD, SPD also

  2. (R)-[11C]Verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate-induced status epilepticus

    Increased functionality of efflux transporters at the blood-brain barrier may contribute to decreased drug concentrations at the target site in CNS diseases like epilepsy. In the rat, pharmacoresistant epilepsy can be mimicked by inducing status epilepticus by intraperitoneal injection of kainate, which leads to development of spontaneous seizures after 3 weeks to 3 months. The aim of this study was to investigate potential changes in P-glycoprotein (P-gp) expression and functionality at an early stage after induction of status epilepticus by kainate. (R)-[11C]verapamil, which is currently the most frequently used positron emission tomography (PET) ligand for determining P-gp functionality at the blood-brain barrier, was used in kainate and saline (control) treated rats, at 7 days after treatment. To investigate the effect of P-gp on (R)-[11C]verapamil brain distribution, both groups were studied without or with co-administration of the P-gp inhibitor tariquidar. P-gp expression was determined using immunohistochemistry in post mortem brains. (R)-[11C]verapamil kinetics were analyzed with approaches common in PET research (Logan analysis, and compartmental modelling of individual profiles) as well as by population mixed effects modelling (NONMEM). All data analysis approaches indicated only modest differences in brain distribution of (R)-[11C]verapamil between saline and kainate treated rats, while tariquidar treatment in both groups resulted in a more than 10-fold increase. NONMEM provided most precise parameter estimates. P-gp expression was found to be similar for kainate and saline treated rats. P-gp expression and functionality does not seem to change at early stage after induction of anticipated pharmacoresistant epilepsy by kainate

  3. Nonkonvulsif Status Epileptikus

    Ayhan AKÖZ; ÖZEL, Lütfi; Bayramoğlu, Atıf; Saritemur, Murat; Recep DEMİR; Zeynep GÖKCAN ÇAKIR

    2013-01-01

    Status epilepticus (SE) can be divided into two subgroups, convulsive status epilepticus (CSE) and nonconvulsive status epilepticus (NCSE). NCSE is clinically characterized by recurrence or persistence of absence or complex partial seizures which unconsciousness persists. Seizures are lasted more than 30 minutes, and accompanied by mental and behavioral changes. Although the main feature is the change of level of consciousness, affective, memory, cognitive, speech, motor systems, behavioral a...

  4. EEG Diagnosis and Clinical Treatment of Electrical Status Epilepticus during Sleep%睡眠中癫痫性电持续状态的脑电诊断及临床治疗

    曹晓春; 刘希娟; 丁勇民; 宋小华; 刘燕玲; 叶春风; 李国林; 刘洋; 龚丹

    2015-01-01

    目的:探讨睡眠中癫痫性电持续状态(electrical status epilepticus during sleep,ESES)的脑电诊断及临床治疗。方法脑电图棘慢波指数(SWI)≥50%并完成治疗的癫痫患儿30例(A 组16例:50%≤SWI<85%;B 组14例:SWI≥85%),按就诊顺序随机分为 C、D 2组,每组15例,行不同疗程(C 组6个月,D 组12个月)激素治疗,治疗前后均进行神经心理损伤评估,并随访治疗后的疗效及不良反应。结果A、B 2组治疗前均有程度不一的神经心理损伤,言语智商(VIQ)、操作智商(PIQ)及总智商(FIQ)均较正常值低,以 VIQ 下降最显著,B 组 VIQ 和 FIQ较 A 组低,差异有统计学意义(P <0.05);C、D 组 VIQ、FIQ 较激素治疗前均有增高(P <0.05),其中 ESES 消失者VIQ、FIQ 明显高于治疗前(P <0.05),但 C、D 2组间神经心理损伤改善程度及总有效率比较差异无统计学意义(P >0.05);D 组不良反应大于 C 组(P <0.05)。结论SWI≥50%定为 ESES 的脑电诊断标准有助于 ESES 的合理诊断,早期干预;激素治疗 ESES 安全有效,疗程6个月更合理。%ABSTRACT:Objective To investigate the EEG diagnosis and clinical treatment of electrical sta-tus epilepticus during sleep(ESES).Methods According to the spike-wave index(SWI),30 chil-dren with epilepsy were divided into group A(50% ≤ SWI0.05).Conclusion The criterion of SWI≥50%contributes to the reasonable diagnosis and early intervention of ESES.Hormone treatment for 6 months is effective and reasonable for ESES.

  5. Increased expression of the chemokines CXCL1 and MIP-1α by resident brain cells precedes neutrophil infiltration in the brain following prolonged soman-induced status epilepticus in rats

    Koemeter-Cox Andrew I

    2011-05-01

    Full Text Available Abstract Background Exposure to the nerve agent soman (GD causes neuronal cell death and impaired behavioral function dependent on the induction of status epilepticus (SE. Little is known about the maturation of this pathological process, though neuroinflammation and infiltration of neutrophils are prominent features. The purpose of this study is to quantify the regional and temporal progression of early chemotactic signals, describe the cellular expression of these factors and the relationship between expression and neutrophil infiltration in damaged brain using a rat GD seizure model. Methods Protein levels of 4 chemokines responsible for neutrophil infiltration and activation were quantified up to 72 hours in multiple brain regions (i.e. piriform cortex, hippocampus and thalamus following SE onset using multiplex bead immunoassays. Chemokines with significantly increased protein levels were localized to resident brain cells (i.e. neurons, astrocytes, microglia and endothelial cells. Lastly, neutrophil infiltration into these brain regions was quantified and correlated to the expression of these chemokines. Results We observed significant concentration increases for CXCL1 and MIP-1α after seizure onset. CXCL1 expression originated from neurons and endothelial cells while MIP-1α was expressed by neurons and microglia. Lastly, the expression of these chemokines directly preceded and positively correlated with significant neutrophil infiltration in the brain. These data suggest that following GD-induced SE, a strong chemotactic response originating from various brain cells, recruits circulating neutrophils to the injured brain. Conclusions A strong induction of neutrophil attractant chemokines occurs following GD-induced SE resulting in neutrophil influx into injured brain tissues. This process may play a key role in the progressive secondary brain pathology observed in this model though further study is warranted.

  6. Alpha-Linolenic Acid-Induced Increase in Neurogenesis is a Key Factor in the Improvement in the Passive Avoidance Task After Soman Exposure.

    Piermartiri, Tetsade C B; Pan, Hongna; Chen, Jun; McDonough, John; Grunberg, Neil; Apland, James P; Marini, Ann M

    2015-09-01

    Exposure to organophosphorous (OP) nerve agents such as soman inhibits the critical enzyme acetylcholinesterase (AChE) leading to excessive acetylcholine accumulation in synapses, resulting in cholinergic crisis, status epilepticus and brain damage in survivors. The hippocampus is profoundly damaged after soman exposure leading to long-term memory deficits. We have previously shown that treatment with three sequential doses of alpha-linolenic acid, an essential omega-3 polyunsaturated fatty acid, increases brain plasticity in naïve animals. However, the effects of this dosing schedule administered after a brain insult and the underlying molecular mechanisms in the hippocampus are unknown. We now show that injection of three sequential doses of alpha-linolenic acid after soman exposure increases the endogenous expression of mature BDNF, activates Akt and the mammalian target of rapamycin complex 1 (mTORC1), increases neurogenesis in the subgranular zone of the dentate gyrus, increases retention latency in the passive avoidance task and increases animal survival. In sharp contrast, while soman exposure also increases mature BDNF, this increase did not activate downstream signaling pathways or neurogenesis. Administration of the inhibitor of mTORC1, rapamycin, blocked the alpha-linolenic acid-induced neurogenesis and the enhanced retention latency but did not affect animal survival. Our results suggest that alpha-linolenic acid induces a long-lasting neurorestorative effect that involves activation of mTORC1 possibly via a BDNF-TrkB-mediated mechanism. PMID:25920465

  7. Salicylic acid-induced glutathione status in tomato crop and resistance to root-knot nematode, Meloidogyne incognita (Kofoid & White Chitwood

    Hari C. Meher

    2011-10-01

    Full Text Available Salicylic acid-(SA is a plant defense stimulator. Exogenous application of SA might influence the status of glutathione-(GSH. GSH activates and SA alters the expression of defense genes to modulate plant resistance against pathogens. The fate of GSH in a crop following SA treatment is largely unknown. The SA-induced profiles of free reduced-, free oxidized-(GSSG and protein bound-(PSSG glutathione in tomato crop following foliar treatment of transplant at 5.0-10.0 μg mL–1 were measured by liquid chromatography. Resistance to root-knot nematode, Meloidogyne incognita damaging tomato and crop performance were also evaluated. SA treatment at 5.0-10.0 μg mL–1 to tomato transplants increased GSH, GSSG and PSSG in plant leaf and root, more so in leaf, during crop growth and development. As the fruits ripened, GSH and PSSG increased and GSSG declined. SA reduced the root infection by M. incognita, nematode reproduction and thus, improved the resistance of tomato var. Pusa Ruby, but reduced crop growth and redox status. SA at 5.0 μg mL–1 improved yield and fruit quality. The study firstly linked SA with activation of glutathione metabolism and provided an additional dimension to the mechanism of induced resistance against obligate nematode pathogen. SA increased glutathione status in tomato crop, imparted resistance against M. incognita, augmented crop yield and functional food quality. SA can be applied at 5.0 μg mL–1 for metabolic engineering of tomato at transplanting to combine host-plant resistance and health benefits in formulating a strategic nematode management decision.

  8. 中老年复杂部分性发作癫痫持续状态的临床特征及误诊分析%Complex partial status epilepticus in the elderly: clinical features and causes of misdiagnosis

    刘晓蓉; 宋兴旺; 常好会; 王玉良; 邹欣

    2009-01-01

    Objective To investigate the clinical features and causes of misdiagnosis of complex partial status epilepticus (CPSE) in the elderly. Methods The clinical data of elderly patients with CPSE admitted in our department between January and December, 2008 with previous misdiagnosis were reviewed. The diagnosis of CPSE was established according to the diagnostic criteria of the International League Against Epilepsy (ILAE). All the patients underwent video-EEG examination, head magnetic resonance imaging (MRI), and routine biochemical examination, and were followed up for at least 3 months. Results Seven female CPSE patients were involved in this analysis including 2 with frontal lobe epilepsy and 5 with temporal lobe epilepsy. The conditions were misdiagnosed as a variety of diseases including Alzheimer's disease, cerebral infarction, coronary heart disease, encephalitis, hysterism, and schizophrenia, and the duration of the misdiagnoses ranged from 2 days to 40 years. Video-EEG showed slow background, continuous interictal discharges or high-voltage slow waves in the temporal or frontal lobe, or ictal discharges of complex partial seizures. After treatment with antiepileptic medications, 3 patients were free of epileptic episodes within 3 months, 3 still remained in complex partial status, and 1 had repeated CPSE. Conclusions Complex symptoms, atypical EEG, co-morbidity and social factors all contribute to misdiagnosis of CPSE in the elderly. Suspected patients should undergo video-EEG examination for a definite diagnosis as early as possible.%目的 分析中老年复杂部分性发作癫痫持续状态(CPSE)的临床特点及误诊原因.方法 收集广州医学院第二附属医院神经内科自2008年1月至12月收治、曾被外院误诊的中老年CPSE患者的临床资料,进行视频脑电图(EEG)、头颅MR、生化检查,根据国际抗癫痫联盟的CPSE诊断标准进行诊断,并随访3个月以上. 结果 本组患者7例,均

  9. Alterações agudas dos níveis de neurotransmissores em corpo estriado de ratos jovens após estado epiléptico induzido por pilocarpina Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status epilepticus

    Rivelilson Mendes de Freitas

    2003-06-01

    Full Text Available Altas doses de agonista colinérgico muscarínico, pilocarpina, produzem alterações comportamentais, convulsões e estado epiléptico em ratos. O objetivo desse estudo foi verificar as alterações nas concentrações dos neurotransmissores em corpo estriado de ratos em desenvolvimento após estado epiléptico induzido pela pilocarpina. Ratas Wistar foram tratadas com uma única dose de pilocarpina (400mg/Kg; s.c.. Controles receberam salina. A concentração dos neurotransmissores foi determinada através do HPLC, no corpo estriado de ratos que no período de observação de 1 e 24h desencadearam estado epiléptico e não sobreviveram à fase aguda do quadro convulsivo. Foi observada redução nos níveis de dopamina, serotonina, ácido dihidroxifenilacético, ácido 5-hidroxiindolacético, e aumento no ácido 4-hidroxi-3-metoxi-fenilacético. Os resultados mostraram que a ativação do sistema colinérgico pode interagir com os sistemas dopaminérgico e serotonérgico nos mecanismos referentes à fase aguda do processo convulsivo.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

  10. Behandlingsrefraktaert status epilepticus med letal rabdomyolyse

    Kreft, Andreas; Rasmussen, Niels; Hansen, Lars Kjaersgård

    2008-01-01

    approximately one day both developed severe rhabdomyolysis with progressive DIC and acute renal failure, causing death despite intensive care, including acute hemodialysis. The aim of this case report is to emphasise one of the rare but severe consequences of SE and also to suggest that patients with known...

  11. Neurogenesis and neuronal regeneration in status epilepticus

    Rotheneichner, Peter; Marschallinger, Julia; Couillard-Despres, Sebastien; Aigner, Ludwig

    2013-01-01

    Neurogenesis in the adult central nervous system has been well documented in several mammals including humans. By now, a plethora of data has been generated with the aim of understanding the molecular and cellular events governing neurogenesis. This growing comprehension will provide the basis for modulation of neurogenesis for therapeutic purposes, in particular in neurodegenerative diseases. Herein, we review the current knowledge on neurogenesis, in particular in the frame of epilepsy, sin...

  12. Hippocampal neuropathology of domoic acid-induced epilepsy in California sea lions (Zalophus californianus)

    Buckmaster, Paul S.; Wen, Xiling; TOYODA, Izumi; Gulland, Frances M. D.; Van Bonn, William

    2014-01-01

    California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Ni...

  13. Establishment of post-status epilepticus model of temporal lobe epilepsy induced by electrical stimulation of the amygdala in rats and spontaneous recurrent seizures%大鼠杏仁核电刺激癫痫持续状态模型的建立及其自发性反复癫痫发作的研究

    齐兆鹏; 金澎; 刘占涛; 孙鹏; 苏明明

    2011-01-01

    Objective To establish a reliable post-status epilepticus model of temporal lobe epilepsy in rats that mimics human temporal lobe epilepsy, and observe the occurrence of spontaneous recurrent seizures (SRS). Methods Status epilepticus which was monitored for 3 h was induced by a 20-min stimulation of the amygdala ( 100 ms train of 1 ms, 60 Hz bipolar pulses, 400 μA, every 0. 5 s). Stimulated rats ( n =21 ) were monitored with a video recording system for the 3-months follow-up period to record the appearance of SRS. Results SRS (total number 181 ) were detected in 14 of the 21 animals (67%) after a latency period of 8 to 73 days (mean 43 days), including 10 times of stage 3 seizure (5.53%), 77 times of stage 4 seizure (42. 54% ), and 94 times of stage 5 seizure (51.93%). Of all the 14 rats, the seizure number beyond 30 was observed in 3 animals, from 20 to 30 in one animal, from 10 to 20 in 2 animals, between 5 and 10 in 2 animals, and less than 5 in 6 animals. Seventy-three percent of SRS appeared during daytime (07: 00-19: 00) and 74 percent of secondarily generalized seizures occurred during daytime. Conclusion This study has been successfully designed to develop a post-status epilepticus animal model induced by electrical stimulation of the amygdale.%目的 建立癫痫持续状态后颞叶癫痫模型,观察大鼠自发性反复发作(SRS)。方法 持续电刺激大鼠杏仁核20 min(单相方波,强度400μA,波宽1 ms,串长100 ms,串隔0.5s,频率60Hz)引发癫痫持续状态(SE),随后进行3h的SE观察,包括大鼠行为表现和脑电变化。SE状态引出后,进行3个月的视频监测,观察大鼠自发性发作的发作情况并进行分组。结果 经过为期3个月的视频观察,出现SRS14只(67%);未出现者7只(33%)。共记录到3~5级发作181次。其中3级发作10次(5.53%),4级发作77次(42.54%),5级发作94次(51.93%)。发作在30次以上者3只;20 ~ 30次者1只;10 ~20次者2只,5~10次者2只;5

  14. Valproic Acid Induced Hyperammonaemic Encephalopathy

    Objective: To observe clinical and laboratory features of valproic acid-induced hyperammonaemic encephalopathy in patients taking valproic acid. Methods: Observational study was conducted at the Neurology Department, Dow University of Health Sciences, Civil Hospital, Karachi, from February 26, 2010 to March 20, 2011. Ten patients on valproic acid therapy of any age group with idiopathic or secondary epilepsy, who presented with encephalopathic symptoms, were registered and followed up during the study. Serum ammonia level, serum valproic acid level, liver function test, cerebrospinal fluid examination, electroencephalogram and brain imaging of all the patients were done. Other causes of encephalopathy were excluded after clinical and appropriate laboratory investigations. Microsoft Excel 2007 was used for statistical analysis. Results: Hyperammonaemia was found in all patients with encephalopathic symptoms. Rise in serum ammonia was independent of dose and serum level of valproic acid. Liver function was also found to be normal in 80% (n=8) of the patients. Valproic acid was withdrawn in all patients. Three (30%) patients improved only after the withdrawal of valproic acid. Six (60%) patients improved after L-Carnitine replacement, one (10%) after sodium benzoate. On followup, serum ammonia had reduced to normal in five (50%) patients and to more than half of the baseline level in two (20%) patients. Three (30%) patients were lost to followup after complete clinical improvement. Conclusion: Within therapeutic dose and serum levels, valproic acid can cause symptomatic hyperammonaemia resulting in encephalopathy. All patients taking valproic acid presenting with encephalopathic symptoms must be monitored for the condition. (author)

  15. FREQUENCY, ETIOLOGY AND IMMEDIATE OUTCOME OF CHILDREN ADMITTED TO PEDIATRIC INTENSIVE CARE UNIT (PICU) WITH CONVULSIVE STATUS EPI LEPTICUS IN KASHMIR NORTH INDIA

    Muzafar; Suhail; Sartaj; Waseem; Aliya; Mudasir

    2015-01-01

    BACKGROUND: Convulsive status epilepticus (CSE) is one of the common causes of childhood hospitalization to PICU with significant morbidity and mortality. Objective of current study was to know the Frequency, etiology and immediate outcome of children admitted to Pediatric Intensive Care Unit (PICU) with convulsive Status Epilepticus in Kashmir Nor...

  16. Valproic acid induced pancreatitis: a case report

    Bhupen Barman

    2014-08-01

    Full Text Available Valproic acid is a commonly used antiepileptic drug. Apart from its common side effect there is definite association between valproic acid therapy and acute pancreatitis. Since 1979, many cases of acute pancreatitis induced by valproic acid have been published in medical literature. Here we are reporting a case of valproic acid induced acute pancreatitis in a 27 years old boy. The treatment is supportive, re-challenge is hazardous and should be avoided. [Int J Res Med Sci 2014; 2(4.000: 1765-1767

  17. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

    Muhammad Nazrul Somchit

    2014-12-01

    Full Text Available Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model. Methods: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day. Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN and creatinine activities were measured. Results: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine. Conclusion: Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.

  18. Status of memory loss.

    Iyer, Parameswaran Mahadeva

    2012-01-01

    A 72-year-old woman presented with first onset of seizure with no prior history of cognitive dysfunction. EEG revealed focal non-convulsive status epilepticus. MRI brain showed a left temporal non-enhancing lesion. Temporal pole biopsy showed acute neuronal necrosis and astrocyte hyperplasia together with extensive amyloid plaques and neurofibrillary tangles. Perivascular oligodendroglial hyperplasia was present. Postmortem examination revealed extensive plaque and tangle disease. Perivascular oligodendroglial hyperplasia was limited to the left temporal area. The presence of focal perivascular oligodendroglial hyperplasia in the left temporal cortex, combined with extensive plaque and tangle disease may have contributed to the focal status epilepticus in this patient. Although the presence of focal perivascular oligodendroglial hyperplasia has been reported in cases of temporal lobe epilepsy, it has not been reported as a cause of seizure in patients with Alzheimer\\'s disease previously. Further studies for clinical-pathologic correlation would be required to confirm this hypothesis.

  19. Clinical Characteristics and Prognosis of Idiopathic Occipital Epilepsy and Electrical Status Epilepticus in Sleeping Children%特发性儿童枕叶癫(癎)伴睡眠期癫(癎)性电持续状态的临床特征及预后

    张胜; 罗序峰; 付四毛; 朱建平; 吴涛

    2012-01-01

    Objective To investigate the clinical manifestations, electroencephalogram(EEG) characteristics, treatment response and prognosis of children with idiopathic occipital epilepsy and electrical status epilepticus in sleep (ESES) . Methods Clinical and EEG data of 8 cases with idiopathic occipital epilepsy and ESES were analyzed together with follow - up for treatment and prognosis. Results The onset age varied from 5 years and 8 months to 8 years and 4 months in the 8 cases. All the 8 cases had neuropsychological injury and motor regression, but had no history of family epilepsy and clear abnormalities by brain imaging examination. Seven patients had seizures, performing exercise - induced limited seizures after waking up; seizures could also attack during awaking period ,including exercise - induced limited seizures (5/7 cases) and overall tonic -clonic seizures (2/7 cases). Antiepileptic drugs (AEDs) reduced attacks in 4 cases,but did not improve the psychological damage to nerve and motor rcgression obviously. Mild improvement in neuropsychological injury and EEG were observed in 3 cases treated with single drug Oxcarbazepine ( OXC). Six cases, who were treated with intravenous methylprednisolone shock therapy, had ideal control, and 1 case had marked improvement of nerve injury and psychological setback in movement. Eight patients were followed up by EEG for 0. 5 -2. 0 years,and 2 cases improved in ESES phenomenon. Up to follow - up,the 8 cases of patients still had mental retardation compared with healthy children in the same age. Conclusions Idiopathic occipital epilepsy is an age - dependent benign epilepsy in children; AEDs are often ineffective when the EEG showes ESES of the patients; hormones can reduce the clinical attack, but can not improve the psychological nerve damage and phenomenon of EEG ESES. Children with poor response to corticosteroids can be treated with OXC monothe-rapy or combined therapy.%目的 探讨特发性枕叶癫(癎)伴睡眠期

  20. Transient changes in the limbic histaminergic system after systemic kainic acid-induced seizures.

    Lintunen, Minnamaija; Sallmen, Tina; Karlstedt, Kaj; Panula, Pertti

    2005-10-01

    Increased brain histamine is reported to protect against convulsions. We used systemic kainic acid (KA) administration to study possible changes of the histaminergic system in rat brain in status epilepticus (SE). Robust increases in brain histamine concentrations and numbers of histamine-immunoreactive nerve fibers were detected in the piriform cortex (Pir) and amygdala after KA injection, suggesting a reactive increase, which is opposite to other published aminergic transmitter responses. These changes, lasting several weeks, might be coupled to a mechanism unrelated to the anticonvulsive function of histamine. Transient increases in mRNA expression of H(3) receptor isoforms with a full-length third intracellular loop, coupled to mitogen-activated protein kinase pathway, were detected first in the hippocampal CA3c area, followed by the Pir and amygdala and then the hippocampal CA1 area. These results suggest that histamine and H3 receptors, which also control the release of GABA and glutamate, might be involved in convulsive SE. PMID:16137576

  1. Absence status associated with focal activity and polydipsia-induced hyponatremia

    Azuma, Hideki

    2008-01-01

    Hideki Azuma, Tatsuo Akechi, Toshi A FurukawaDepartment of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanAbstract: We report a case of de novo absence status associated with focal discharge and polydipsia-induced hyponatremia. Nonconvulsive status epilepticus (NCSE) is classified as absence status or complex partial status. Absence status is characterized by bilateral synchronized spike and wave complex bursts and a vari...

  2. Acid-induced changes of brain protein buffering

    Kraig, Richard P.; Wagner, Robert J.

    1987-01-01

    Excessive cellular acidosis is thought to enhance destruction of brain from ischemia. Protein denaturation may contribute to such injury although the behavior of brain proteins to acidosis is poorly defined. As a first approach to detect acid-induced changes in brain proteins and to characterize buffer content, homogenates were acidified for 20 min (as low as pH 3.1), returned to baseline pH (6.9), and then titrated. Titration curves show a significant (P < 0.0001) and permanent increase in b...

  3. Increased isoprostane levels in oleic acid-induced lung injury

    Ono, Koichi [Department of Anesthesiology and Resuscitation, Shinshu University School of Medicine, Matsumoto (Japan); Koizumi, Tomonobu, E-mail: tomonobu@shinshu-u.ac.jp [First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto (Japan); Tsushima, Kenji; Yoshikawa, Sumiko; Yokoyama, Toshiki [First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto (Japan); Nakagawa, Rikimaru [Department of Anesthesiology and Resuscitation, Shinshu University School of Medicine, Matsumoto (Japan); Obata, Toru [Department of Molecular Cell Biology, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo (Japan)

    2009-10-16

    The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2{alpha}). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

  4. Sphingoid bases inhibit acid-induced demineralization of hydroxyapatite.

    Valentijn-Benz, Marianne; van 't Hof, Wim; Bikker, Floris J; Nazmi, Kamran; Brand, Henk S; Sotres, Javier; Lindh, Liselott; Arnebrant, Thomas; Veerman, Enno C I

    2015-01-01

    Calcium hydroxyapatite (HAp), the main constituent of dental enamel, is inherently susceptible to the etching and dissolving action of acids, resulting in tooth decay such as dental caries and dental erosion. Since the prevalence of erosive wear is gradually increasing, there is urgent need for agents that protect the enamel against erosive attacks. In the present study we studied in vitro the anti-erosive effects of a number of sphingolipids and sphingoid bases, which form the backbone of sphingolipids. Pretreatment of HAp discs with sphingosine, phytosphingosine (PHS), PHS phosphate and sphinganine significantly protected these against acid-induced demineralization by 80 ± 17%, 78 ± 17%, 78 ± 7% and 81 ± 8%, respectively (p < 0.001). On the other hand, sphingomyelin, acetyl PHS, octanoyl PHS and stearoyl PHS had no anti-erosive effects. Atomic force measurement revealed that HAp discs treated with PHS were almost completely and homogeneously covered by patches of PHS. This suggests that PHS and other sphingoid bases form layers on the surface of HAp, which act as diffusion barriers against H(+) ions. In principle, these anti-erosive properties make PHS and related sphingosines promising and attractive candidates as ingredients in oral care products. PMID:25300299

  5. Metformin protects rat hepatocytes against bile acid-induced apoptosis.

    Titia E Woudenberg-Vrenken

    Full Text Available BACKGROUND: Metformin is used in the treatment of Diabetes Mellitus type II and improves liver function in patients with non-alcoholic fatty liver disease (NAFLD. Metformin activates AMP-activated protein kinase (AMPK, the cellular energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an inhibitor of mammalian target of rapamycin (mTOR. Both AMPK and mTOR are able to modulate cell death. AIM: To evaluate the effects of metformin on hepatocyte cell death. METHODS: Apoptotic cell death was induced in primary rat hepatocytes using either the bile acid glycochenodeoxycholic acid (GCDCA or TNFα in combination with actinomycin D (actD. AMPK, mTOR and phosphoinositide-3 kinase (PI3K/Akt were inhibited using pharmacological inhibitors. Apoptosis and necrosis were quantified by caspase activation, acridine orange staining and Sytox green staining respectively. RESULTS: Metformin dose-dependently reduces GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing necrotic cell death. Metformin does not protect against TNFα/ActD-induced apoptosis. The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not inhibit NF-κB activation. CONCLUSION: Metformin protects against bile acid-induced apoptosis and could be considered in the treatment of chronic liver diseases accompanied by inflammation.

  6. Nonconvulsive status epilepticus and Creutzfeldt–Jakob-like EEG changes in a case of lithium toxicity

    B.K. Madhusudhan

    2014-01-01

    This case highlights the importance of therapeutic drug-level monitoring of lithium, especially where toxicity is suspected, and the important role electroencephalography plays in diagnosing NCSE and its management.

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

    Suchomelová, L.; Lopes-Meraz, M. L.; Niquet, J.; Kubová, Hana; Wasterlain, C. G.

    2015-01-01

    Roč. 305, Oct 1 (2015), s. 209-224. ISSN 0306-4522 R&D Projects: GA ČR(CZ) GAP302/10/0971; GA MŠk(CZ) ME08045; GA MŠk(CZ) LC554 Institutional support: RVO:67985823 Keywords : neuronal injury * temperature * immature brain * lithium/pilocarpine model * EEG monitoring Subject RIV: FH - Neurology Impact factor: 3.357, year: 2014

  8. Brain metabolism and diffusion in the rat cerebral cortex during pilocarpine-induced status epilepticus

    Šlais, Karel; Voříšek, Ivan; Zoremba, N.; Homola, Aleš; Dmytrenko, Lesia; Syková, Eva

    2008-01-01

    Roč. 209, č. 1 (2008), s. 145-154. ISSN 0014-4886 R&D Projects: GA MŠk 1M0538; GA MŠk(CZ) LC554 Grant ostatní: EU(DE) 512146 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703 Source of funding: R - rámcový projekt EK Keywords : Diffusion * Microdialysis * Pilocarpine Subject RIV: FH - Neurology Impact factor: 3.974, year: 2008

  9. Rare presentation of a common disease: Idiopathic hypoparathyroidism presenting with extrapyramidal symptoms and status epilepticus

    Kaushik Ghosh

    2012-01-01

    Full Text Available We report of an 18-year-old male who presented with an epileptiform disorder, features of hypocalcemia, and an extrapyramidal symptom in the form of choreoathetosis. On evaluation he had idiopathic hypoparathyroidism with extensive calcifications in the extrapyramidal system of the brain; basal ganglion, as well as in the cerebral cortex and cerebellum, which is a rare entity. We report the rare presentation of a common disorder, which requires to be considered in evaluating hypoparathyroidism.

  10. Status epilepticus induces changes in the expression and localization of endogenous palmitoyl-protein thioesterase 1.

    Suopanki, J; Lintunen, M; Lahtinen, H; Haltia, M; Panula, P; Baumann, M; Tyynelä, J

    2002-08-01

    Kainic acid (KA)-induced experimental epilepsy, a model of excitotoxicity, leads to selective neuronal death and synaptic restructuring. We used this model to investigate the effects of neuronal hyperactivation on palmitoyl-protein thioesterase 1 (PPT1), the deficiency of which causes drastic neurodegeneration. Immunological stainings showed that epileptic seizures in adult rats led to a progressive and remarkable increase of PPT1 in limbic areas of the brain. Within 1 week, the maximal expression was observed in CA3 and CA1 pyramidal neurons of the hippocampus. In the surviving pyramidal neurons, PPT1 localized in vesicular structures in cell soma and neuritic extensions. After seizures, colocalization of PPT1 with synaptic membrane marker (NMDAR2B) was enhanced. Further, synaptic fractionation revealed that after seizures PPT1 was readily observed on the presynaptic side of synaptic junction. These data suggest that PPT1 may protect neurons from excitotoxicity and have a role in synaptic plasticity. PMID:12270687

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

    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

  12. Delays and Factors Related to Cessation of Generalized Convulsive Status Epilepticus.

    Kämppi, Leena; Ritvanen, Jaakko; Mustonen, Harri; Soinila, Seppo

    2015-01-01

    Introduction. This study was designed to identify the delays and factors related to and predicting the cessation of generalized convulsive SE (GCSE). Methods. This retrospective study includes 70 consecutive patients (>16 years) diagnosed with GCSE and treated in the emergency department of a tertiary hospital over 2 years. We defined cessation of SE stepwise using clinical seizure freedom, achievement of burst-suppression, and return of consciousness as endpoints and calculated delays for these cessation markers. In addition 10 treatment delay parameters and 7 prognostic and GCSE episode related factors were defined. Multiple statistical analyses were performed on their relation to cessation markers. Results. Onset-to-second-stage-medication (p = 0.027), onset-to-burst-suppression (p = 0.005), and onset-to-clinical-seizure-freedom (p = 0.035) delays correlated with the onset-to-consciousness delay. We detected no correlation between age, epilepsy, STESS, prestatus period, type of SE onset, effect of the first medication, and cessation of SE. Conclusion. Our study demonstrates that rapid administration of second-stage medication and early obtainment of clinical seizure freedom and burst-suppression predict early return of consciousness, an unambiguous marker for the end of SE. We propose that delays in treatment chain may be more significant determinants of SE cessation than the previously established outcome predictors. Thus, streamlining the treatment chain is advocated. PMID:26347816

  13. Delays and Factors Related to Cessation of Generalized Convulsive Status Epilepticus

    Leena Kämppi

    2015-01-01

    Full Text Available Introduction. This study was designed to identify the delays and factors related to and predicting the cessation of generalized convulsive SE (GCSE. Methods. This retrospective study includes 70 consecutive patients (>16 years diagnosed with GCSE and treated in the emergency department of a tertiary hospital over 2 years. We defined cessation of SE stepwise using clinical seizure freedom, achievement of burst-suppression, and return of consciousness as endpoints and calculated delays for these cessation markers. In addition 10 treatment delay parameters and 7 prognostic and GCSE episode related factors were defined. Multiple statistical analyses were performed on their relation to cessation markers. Results. Onset-to-second-stage-medication (p=0.027, onset-to-burst-suppression (p=0.005, and onset-to-clinical-seizure-freedom (p=0.035 delays correlated with the onset-to-consciousness delay. We detected no correlation between age, epilepsy, STESS, prestatus period, type of SE onset, effect of the first medication, and cessation of SE. Conclusion. Our study demonstrates that rapid administration of second-stage medication and early obtainment of clinical seizure freedom and burst-suppression predict early return of consciousness, an unambiguous marker for the end of SE. We propose that delays in treatment chain may be more significant determinants of SE cessation than the previously established outcome predictors. Thus, streamlining the treatment chain is advocated.

  14. Status epilepticus in immature rats leads to behavioural and cognitive impairment and epileptogenesis

    Kubová, Hana; Mareš, Pavel; Suchomelová, Lucie; Brožek, Gustav; Druga, Rastislav; Pitkanen, A.

    2004-01-01

    Roč. 19, č. 12 (2004), s. 3255-3265. ISSN 0953-816X R&D Projects: GA MZd NF6474; GA ČR GA309/01/0285 Institutional research plan: CEZ:AV0Z5011922 Keywords : epilepsy * elevated plus-maze * Morris water-maze Subject RIV: FH - Neurology Impact factor: 3.820, year: 2004

  15. Interstrain differences in cognitive functions in rats in relation to status epilepticus

    Hort, J.; Brožek, Gustav; Komárek, V.; Langmeier, M.; Mareš, Pavel

    2000-01-01

    Roč. 112, - (2000), s. 77-83. ISSN 0166-4328 R&D Projects: GA MZd IZ2904; GA MZd IZ3510; GA AV ČR KSK2011602 Grant ostatní: GA UK(XC) 25/1966 Subject RIV: ED - Physiology Impact factor: 2.263, year: 2000

  16. The BRPF2/BRD1-MOZ complex is involved in retinoic acid-induced differentiation of embryonic stem cells.

    Cho, Hye In; Kim, Min Seong; Jang, Yeun Kyu

    2016-08-01

    The scaffold protein BRPF2 (also called BRD1), a key component of histone acetyltransferase complexes, plays an important role in embryonic development, but its function in the differentiation of embryonic stem cells (ESCs) remains unknown. In the present study, we investigated whether BRPF2 is involved in mouse ESC differentiation. BRPF2 depletion resulted in abnormal formation of embryoid bodies, downregulation of differentiation-associated genes, and persistent maintenance of alkaline phosphatase activity even after retinoic acid-induced differentiation, indicating impaired differentiation of BRPF2-depleted ESCs. We also found reduced global acetylation of histone H3 lysine 14 (H3K14) in BRPF2-depleted ESCs, irrespective of differentiation status. Further, co-immunoprecipitation analysis revealed a physical association between BRPF2 and the histone acetyltransferase MOZ in differentiated ESCs, suggesting the role of BRPF2-MOZ complexes in ESC differentiation. Together, these results suggest that BRPF2-MOZ complexes play an important role in the differentiation of ESCs via H3K14 acetylation. PMID:27256846

  17. Mefenamic acid-induced neutropenia and renal failure in elderly females with hypothyroidism.

    Handa, S I; FREESTONE, S.

    1990-01-01

    We report mefenamic acid-induced non-oliguric renal failure and severe neutropenia occurring simultaneously in two elderly females. The neutropenia was due to maturation arrest of the myeloid series in one patient. Both patients were also hypothyroid, but it is not clear whether this was a predisposing factor to the development of these adverse reactions. However, it would seem prudent not to use mefenamic acid in hypothyroid patients until the hypothyroidism has been corrected.

  18. The role of MAPK signalling pathways in acetic acid-induced cell death of Saccharomyces cerevisiae

    Azevedo, Flávio Humberto Torres Dias Feio de

    2011-01-01

    Dissertação de mestrado em Genética Molecular Mitogenic Activated Protein Kinase (MAPK) cascades are important signalling pathways that allow yeast cells to swiftly adapt to changing environmental conditions. Previous studies suggested that the High Osmolarity Glycerol (HOG) MAPK pathway and ceramide production are involved in acetic-acid induced apoptosis in yeast. Evidence that changes in the levels of endogenous ceramides can affect yeast cell fate has also been put forth...

  19. Acid mediates a prolonged antinociception via substance P signaling in acid-induced chronic widespread pain

    Chen, Wei-Nan; Chen, Chih-Cheng

    2014-01-01

    Background Substance P is an important neuropeptide released from nociceptors to mediate pain signals. We recently revealed antinociceptive signaling by substance P in acid-sensing ion channel 3 (ASIC3)-expressing muscle nociceptors in a mouse model of acid-induced chronic widespread pain. However, methods to specifically trigger the substance P antinociception were still lacking. Results Here we show that acid could induce antinociceptive signaling via substance P release in muscle. We preve...

  20. Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats.

    Kumar, Hariom; Sharma, Bhupesh

    2016-01-01

    Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism. PMID:26551768

  1. Tiagabine: efficacy and safety in partial seizures – current status

    Jürgen Bauer

    2008-09-01

    Full Text Available Jürgen Bauer, Déirdre Cooper-MahkornDepartment of Epileptology, Bonn University Hospital, GermanyAbstract: Tiagabine hydrochloride (TGB is a selective gamma-aminobutyric acid (GABA reuptake inhibitor. TGB is effective as an add-on medication in adults and children 12 years and older in the treatment of partial seizures. Results of nonrandomized add-on trials with TGB show treatment success with seizure reduction of at least 50% in 33% to 46% of patients. In newly diagnosed patients with partial epilepsy, TGB monotherapy was as effective as carbamazepine. Comedication with TGB elevates the risk of nonconvulsive status (7.8% vs 2.7% without TGB. The most common side effects include dizziness/lightheadedness, asthenia/lack of energy and somnolence. TGB has no negative effects on cognition; it does not increase the risk of fractures or rash. TGB may interfere with color perception. TGB presents an intermediate risk for depression in patients with epilepsy (approximately 4%. Regarding the risk of overdose, 96–680 mg TGB (mean 224 mg caused seizures or coma. TGB is an antiepileptic drug exhibiting a specific anticonvulsive mechanism of action, the efficacy of which is relatively low when used in comedication. Critical side effects, such as the induction of nonconvulsive status epilepticus, further limit its use.Keywords: epilepsy, tiagabine, antiepileptic drugs, status epilepticus, pharmacotherapy

  2. DECREASED APOPTOSIS DURING CAR-MEDIATED HEPATOPROTECTION AGAINST LITHOCHOLIC ACID-INDUCED LIVER INJURY IN MICE

    Beilke, Lisa D.; Aleksunes, Lauren M.; Olson, Erik R.; Besselsen, David G; Klaassen, Curtis D.; Dvorak, Katerina; Cherrington, Nathan J.

    2009-01-01

    Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that is regulated by the constitutive androstane receptor (CAR). Activation of CAR can protect the liver against bile acid-induced toxicity and it may have a role in cell death via apoptosis by altering expression of Bcl-2 family proteins such as myeloid cell leukemia-1 (Mcl-1). Our aim was to determine if activation of CAR reduces hepatocellular apoptosis during cholestasis as a mechanism of hepatoprotection. CAR+/+ (WT) and CAR−/−...

  3. Salivary a-amylase protects enamel surface against acid induced softening

    Lazovic, Maja Bruvo; Moe, Dennis; Kirkeby, Svend;

    -TOF mass fingerprinting following trypsin digestion. Each persistent peak in the HPLC chromatograms was related to the protective effect against acid-induced enamel softening obtained by the corresponding saliva sample by multiple regression analysis. Results: One peak identified as a-amylase had an...... explanatory power of 39% in the analysis with high concentrations being most protective (p<0.001). In addition, a smaller peak retrieved later in the chromatograms also had a strong protective effect. Inclusion of this peak in the analysis increased the explanatory power of amylase on protective effect to 65...

  4. Reduction of sodium deoxycholic acid-induced scratching behaviour by bradykinin B2 receptor antagonists

    Hayashi, Izumi; Majima, Masataka

    1999-01-01

    Subcutaneous injection of sodium deoxycholic acid into the anterior of the back of male ddY mice elicited dose-dependent scratching of the injected site with the forepaws and hindpaws.Up to 100 μg of sodium deoxycholic acid induced no significant increase in vascular permeability at the injection site as assessed by a dye leakage method.Bradykinin (BK) B2 receptor antagonists, FR173657 and Hoe140, significantly decreased the frequency of scratching induced by sodium deoxycholic acid.Treatment...

  5. Luteolin prevents uric acid-induced pancreatic β-cell dysfunction

    Ding, Ying; Shi, Xuhui; Shuai, Xuanyu; Xu, Yuemei; Liu, Yun; Liang, Xiubin; Wei, Dong; Su, Dongming

    2014-01-01

    Abstract Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide (NO) formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor (NF)-κB. Western blotting assays were also performed to a...

  6. Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid-induced excitotoxicity in rat hippocampus.

    Zong, Nan; Li, Fei; Deng, Yuanyuan; Shi, Jingshan; Jin, Feng; Gong, Qihai

    2016-10-15

    Excitotoxicity is one of the most extensively studied causes of neuronal death and plays an important role in Alzheimer's disease (AD). Icariin is a flavonoid component of a traditional Chinese medicine reported to possess a broad spectrum of pharmacological effects. The present study was designed to investigate the effects of icariin against learning and memory impairment induced by excitotoxicity. Here, we demonstrated that rats receiving intracerebroventricular injection of excitatory neurotoxin ibotenic acid exhibited impaired learning and memory. Oral administration of icariin at doses of 20 and 40mg/kg rescued behavioral performance and protected against neurotoxicity in rat hippocampus by suppressing ibotenic acid induced pro-apoptosis. Furthermore, Western blott of hippocampal specimens revealed that icariin up-regulated the expression of calbindin-D28k protein following ibotenic acid administration. Additionally, icariin inhibited mitogen-activated protein kinase (MAPK) family phosphorylation and nuclear factor kappa B (NF-κB) signaling, implicating the MAPK signaling and NF-κB signaling pathways were involved in the mechanism underlying icariin-mediated neuroprotection against ibotenic acid-induced excitotoxicity. These data suggested that icariin could be a potential agent for treatment of excitotoxicity-related diseases, including AD. PMID:27368415

  7. Hepatoprotective effect of vitamin C on lithocholic acid-induced cholestatic liver injury in Gulo(-/-) mice.

    Yu, Su Jong; Bae, Seyeon; Kang, Jae Seung; Yoon, Jung-Hwan; Cho, Eun Ju; Lee, Jeong-Hoon; Kim, Yoon Jun; Lee, Wang Jae; Kim, Chung Yong; Lee, Hyo-Suk

    2015-09-01

    Prevention and restoration of hepatic fibrosis from chronic liver injury is essential for the treatment of patients with chronic liver diseases. Vitamin C is known to have hepatoprotective effects, but their underlying mechanisms are unclear, especially those associated with hepatic fibrosis. Here, we analyzed the impact of vitamin C on bile acid induced hepatocyte apoptosis in vitro and lithocholic acid (LCA)-induced liver injury in vitamin C-insufficient Gulo(-/-) mice, which cannot synthesize vitamin C similarly to humans. When Huh-BAT cells were treated with bile acid, apoptosis was induced by endoplasmic reticulum stress-related JNK activation but vitamin C attenuated bile acid-induced hepatocyte apoptosis in vitro. In our in vivo experiments, LCA feeding increased plasma marker of cholestasis and resulted in more extensive liver damage and hepatic fibrosis by more prominent apoptotic cell death and recruiting more intrahepatic inflammatory CD11b(+) cells in the liver of vitamin C-insufficient Gulo(-/-) mice compared to wild type mice which have minimal hepatic fibrosis. However, when vitamin C was supplemented to vitamin C-insufficient Gulo(-/-) mice, hepatic fibrosis was significantly attenuated in the liver of vitamin C-sufficient Gulo(-/-) mice like in wild type mice and this hepatoprotective effect of vitamin C was thought to be associated with both decreased hepatic apoptosis and necrosis. These results suggested that vitamin C had hepatoprotective effect against cholestatic liver injury. PMID:26057690

  8. Polyunsaturated Branched-Chain Fatty Acid Geranylgeranoic Acid Induces Unfolded Protein Response in Human Hepatoma Cells.

    Chieko Iwao

    Full Text Available The acyclic diterpenoid acid geranylgeranoic acid (GGA has been reported to induce autophagic cell death in several human hepatoma-derived cell lines; however, the molecular mechanism for this remains unknown. In the present study, several diterpenoids were examined for ability to induce XBP1 splicing and/or lipotoxicity for human hepatoma cell lines. Here we show that three groups of diterpenoids emerged: 1 GGA, 2,3-dihydro GGA and 9-cis retinoic acid induce cell death and XBP1 splicing; 2 all-trans retinoic acid induces XBP1 splicing but little cell death; and 3 phytanic acid, phytenic acid and geranylgeraniol induce neither cell death nor XBP1 splicing. GGA-induced ER stress/ unfolded protein response (UPR and its lipotoxicity were both blocked by co-treatment with oleic acid. The blocking activity of oleic acid for GGA-induced XBP1 splicing was not attenuated by methylation of oleic acid. These findings strongly suggest that GGA at micromolar concentrations induces the so-called lipid-induced ER stress response/UPR, which is oleate-suppressive, and shows its lipotoxicity in human hepatoma cells.

  9. Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

    Aleksandra Matuszyk

    2016-01-01

    Full Text Available Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa.

  10. STRUCTURAL REMODELING OF PROTEOGLYCANS UPON RETINOIC ACID-INDUCED DIFFERENTIATION OF NCCIT CELLS*

    Gasimli, Leyla; Stansfield, Hope E.; Nairn, Alison V.; Liu, Haiying; Paluh, Janet L.; Yang, Bo; Dordick, Jonathan S.; Moremen, Kelley W.; Linhardt, Robert J.

    2012-01-01

    Pluripotent and multipotent cells become increasingly lineage restricted through differentiation. Alterations to the cellular proteoglycan composition and structure should accompany these changes to influence cell proliferation, delineation of tissues and acquisition of cell migration capabilities. Retinoic acid plays an important role in pre-patterning of the early embryo. Retinoic acid can be used in vitro to induce differentiation, causing pluripotent and multipotent cells to become increasingly lineage restricted. We examined retinoic acid-induced changes in the cellular proteoglycan composition of the well-characterized teratocarcinoma line NCCIT. Our analysis revealed changes in the abundance of transcripts for genes encoding core proteins, enzymes that are responsible for early and late linkage region biosynthesis, as well as enzymes for GAG chain extension and modification. Transcript levels for genes encoding core proteins used as backbones for polysaccharide synthesis revealed highly significant increases in expression of lumican and decorin, 1500-fold and 2800-fold, respectively. Similarly, glypican 3, glypican 5, versican and glypican 6 showed increases between 5 and 70-fold. Significant decreases in biglycan, serglycin, glypican 4, aggrecan, neurocan, CD74 and glypican 1 were observed. Disaccharide analysis of the glycans in heparin/heparan sulfate and chondroitin/dermatan sulfate revealed retinoic acid-induced changes restricted to chondroitin/dermatan sulfate glycans. Our study provides the first detailed analysis of changes in the glycosaminoglycan profile of human pluripotent cells upon treatment with the retinoic acid morphogen. PMID:23053635