Cockerell, O C; Walker, M C; Sander, J W; Shorvon, S D
Twenty patients with complex partial status epilepticus were identified retrospectively from a specialist neurology hospital. Seventeen patients experienced recurrent episodes of complex partial status epilepticus, often occurring at regular intervals, usually over many years, and while being treated with effective anti-epileptic drugs. No unifying cause for the recurrences, and no common epilepsy aetiologies, were identified. In spite of the frequency of recurrence and length of history, none of the patients showed any marked evidence of cognitive or neurological deterioration. Complex partial status epilepticus is more common than is generally recognised, should be differentiated from other forms of non-convulsive status, and is often difficult to treat. PMID:8021671
Béquet, D; Bodiguel, E; Renard, J L; Goasguen, J
The cases of non convulsive, complex, partial ailment are a cause of a confusional state. Such a case on an adult is here reported, and its clinical presentation was a unvarying forgetfulness together with elements of a frontal syndrome. The aetiology was most probably a viral meningo-encephalitis. Clinical semiology of these "EMPC" is variable, either made of partial, recurrent attacks, sometimes with automatisms, or made of a continuous, possibly fluctuating, confusional state. Attacks shown on the EEG are partial or generalized with a variable start, sometimes bilateral, even continuous or discontinuous. The onset is most often temporal or frontal. The cause is very rarely found out. The evolution is usually good, but extended deficiencies of memory are described, linked to the duration (more than 12 hours) of EMPC. Therefore, the treatment must be precocious using diazepam or phenytoin.
Blumkin, Lubov; Lerman-Sagie, Tally; Houri, Tzion; Gilad, Eli; Nissenkorn, Andrea; Ginsberg, Mira; Watemberg, Nathan
Topiramate was safely administered to two young children with refractory partial status epilepticus via nasogastric tube in rapid titration up to a very high total daily dose. An excellent clinical response occurred in both cases. Reaching high daily doses of topiramate within days allowed for safe discontinuation of other antiepileptic drugs in both patients. Given the high efficacy of rapidly titrated topiramate in our patients, this medication may be useful in some cases of pediatric refractory partial status epilepticus. However, more clinical studies on this therapeutic approach are needed to establish the precise role of topiramate in status epilepticus in children.
Varon, Daniel; Pritchard, Paul B; Wagner, Mark T; Topping, Kris
The characteristic features of Kluver-Bucy syndrome include hypersexuality, hyperorality, placidity, hypermetamorphosis, visual agnosia, changes in dietary habits, and memory impairment. Human cases have been reported with herpes simplex encephalitis, head injury, Pick's disease, transtentorial herniation, adrenoleukodystrophy, and Reye's syndrome, all involving bilateral temporal lobe pathology. We present the case of a patient with no evidence of a structural lesion in the temporal lobes and behavioral changes consistent with Kluver-Bucy syndrome following complex partial status epilepticus.
Hocker, Sara E
Status epilepticus, which is simultaneously a neurologic and systemic emergency, often results in significant disability and may be fatal. This article presents a pragmatic approach to the evaluation and management of status epilepticus in adults for the practicing clinician. Rapid recognition, treatment respecting a written protocol, and careful attention to potential complications may limit sequelae. Studies aimed at earlier identification of etiologies in cryptogenic status epilepticus and improving the treatment of established status epilepticus are urgently needed to limit the development of refractoriness. This article reviews the guidelines and up-to-date information on the use of both pharmacologic and nonpharmacologic therapies in status epilepticus and discusses the shifts in our understanding of the balance between the need for aggressive control of seizures and the risks of treatment. This article also presents a suggested approach to the evaluation and management of common types of status epilepticus and explores future directions.
Delgado, Montserrat G; Vega, Juan; Santamarta, Elena; Caminal, Luis
Few cases of Crohn's disease complicated with meningitis and epidural abscess have been described in literature. We present a case of a 42-year-old former smoker female patient diagnosed with Crohn's disease in September 1995 (with severe nutritional problems). On 20 February 2012, she was admitted due to a probable sepsis (without any previous treatment). After several days she developed a confusion syndrome (probable Wernicke's disease). On 5 March 2012, the patient presented with a febrile episode of 39 ° C. Two days later, the patient presented aphasia and paraparesis, and 3 days later she presented a complex partial status epilepticus. A lumbar puncture was performed and showed 131 leucocytes (63% granulocytes) and proteins 296.3. The abdominopelvic CT scan revealed a presacral collection that seem to extend cranially towards the lumbosacral spine. The lumbar MRI confirmed the lumbar epidural abscess secondary to the fistulisation of the presacral abscess.
Manno, Edward M.
Status epilepticus is a neurological emergency that is commonly encountered by the neurohospitalist. Successful treatment depends upon the recognition of prolonged seizure activity and the acute mobilization of available resources. Pharmacologic treatment regimens have been shown to decrease the time needed for successful control of seizures and have provided for the rapid administration of anticonvulsant medications. Treatment strategies have evolved so that clinicians can administer effective doses of medication by whatever routes of administration are immediately available. Traditional algorithms for the treatment of status epilepticus have used a stepwise approach to the administration of first-, second-, and third-order medications. More recent options have included aggressive anesthetic doses of medications while second-line medications are being titrated. PMID:23983834
Hosford, D A
Nonconvulsive status epilepticus includes three clinical situations: complex partial status epilepticus; absence status epilepticus: and obtundation in the presence of electrographic status epilepticus. Animal models that provide information helpful to clinical management exist for both complex partial and absence status epilepticus. In models of complex partial status epilepticus (pilocarpine, kainic acid, and various protocols using electrical stimulation), neuronal damage in discrete neuronal populations follows an episode of status epilepticus. Hippocampal populations are particularly susceptible to neuropathologic sequelae. Although it is difficult in some cases to distinguish whether the inducing agent or the status epilepticus causes neuropathology, the similar patterns of damage caused by different inducing stimuli provide converging lines of evidence suggesting that the neuropathologic consequences stem at least in part from status epilepticus. In models of absence status epilepticus (genetic mutants, pentylenetetrazole), there is relatively scarce neuropathology that can be attributed directly to status epilepticus. Together these data from animal models suggest that neuropathologic consequences from complex partial status epilepticus may be more severe than those from absence status epilepticus. If these findings translate to patients, then nonconvulsive status epilepticus of the complex partial type should be managed more aggressively than nonconvulsive status epilepticus of the absence type.
Abend, Nicholas S; Loddenkemper, Tobias
Purpose of Review This review discusses management of status epilepticus in children including both anticonvulsant medications and overall management approaches. Recent Findings Rapid management of status epilepticus is associated with a greater likelihood of seizure termination and better outcomes, yet data indicate there are often management delays. This review discusses an overall management approach aiming to simultaneously identify and manage underlying precipitant etiologies, administer anticonvulsants in rapid succession until seizures have terminated, and identify and manage systemic complications. An example management pathway is provided. Summary Status epilepticus is a common neurologic emergency in children and requires rapid intervention. Having a predetermined status epilepticus management pathway can expedite management. PMID:25304961
Abend, Nicholas S; Loddenkemper, Tobias
This review discusses the management of status epilepticus in children, including both anticonvulsant medications and overall management approaches. Rapid management of status epilepticus is associated with a greater likelihood of seizure termination and better outcomes, yet data indicate that there are often management delays. This review discusses an overall management approach aiming to simultaneously identify and manage underlying precipitant causes, administer anticonvulsants in rapid succession until seizures have terminated, and identify and manage systemic complications. An example management pathway is provided. Status epilepticus is a common neurologic emergency in children and requires rapid intervention. Having a predetermined status epilepticus management pathway can expedite management.
Armon, C.; Radtke, R.; Friedman, A.
OBJECTIVES—To report on five patients who developed, 2 to 4 days after an intracranial neurosurgical procedure, new, persistent, focal neurological deficits which were due to inhibitory simple partial (non-convulsive) status epilepticus, and resolved with anticonvulsant treatment. METHODS—The age range of the five patients was 15-74 years. The operations were: aneurysm clipping (three patients) and resections of an oligodendroglioma and a cavernous haemangioma (one patient each). The new focal deficits were: right hemiparesis and aphasia (two patients), aphasia alone (two patients), and left hemiparesis (one patient). The deficits were not explained by CT (obtained in all patients) or cerebral angiography (performed in two). RESULTS—Electroencephalography showed, in all patients, continuous or intermittent focal seizures arising from cortex regionally relevant to the clinical dysfunction. Subtle positive epileptic phenomena (jerking) occurred intermittently in three patients as a late concommitant. Administration of anticonvulsant drugs resulted in significant improvement within 24 hours in four patients, with parallel resolution of ictal EEG activity. The fifth patient improved more slowly. Two patients relapsed when anticonvulsant concentrations fell, and improved again when they were raised. CONCLUSIONS—It is suggested that inhibitory simple partial (non-convulsive) status epilepticus be considered in the differential diagnosis when a new unexplained neurological deficit develops after an intracranial neurosurgical procedure. An EEG may help to diagnose this condition, leading to definitive treatment. PMID:10864598
Betjemann, John P; Lowenstein, Daniel H
Status epilepticus is a common neurological emergency with considerable associated health-care costs, morbidity, and mortality. The definition of status epilepticus as a prolonged seizure or a series of seizures with incomplete return to baseline is under reconsideration in an effort to establish a more practical definition to guide management. Clinical research has focused on early seizure termination in the prehospital setting. The approach of early escalation to anaesthetic agents for refractory generalised convulsive status epilepticus, rather than additional trials of second-line anti-epileptic drugs, to avoid neuronal injury and pharmaco-resistance associated with prolonged seizures is gaining momentum. Status epilepticus is also increasingly identified in the inpatient setting as the use of extended electroencephalography monitoring becomes more commonplace. Substantial further research to enable early identification of status epilepticus and efficacy of anti-epileptic drugs will be important to improve outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.
Carota, Antonio; Novy, Jan; Rossetti, Andrea O
Utilization behavior (UB) consists of reaching out and using objects in the environment in an automatic manner and out of context. This behavior has been correlated to frontal lobe dysfunction, especially of the right hemisphere. We describe a 60-year-old woman, affected by a glioblastoma located in the right frontal region, who presented with intermittent UB of the mobile phone as the main clinical manifestation of partial complex status epilepticus. Video/EEG studies showed a striking correlation between mobile phone utilization and ictal epileptic activity. Clinical and EEG findings were markedly reduced after the introduction of antiepileptic drugs. This case study suggests that UB may be added to the symptoms described for partial seizures originating from frontal areas.
Pichler, M; Hocker, S
Status epilepticus is a neurologic and medical emergency manifested by prolonged seizure activity or multiple seizures without return to baseline. It is associated with substantial medical cost, morbidity, and mortality. There is a spectrum of severity dependent on the type of seizure, underlying pathology, comorbidities, and appropriate and timely medical management. This chapter discusses the evolving definitions of status epilepticus and multiple patient and clinical factors which influence outcome. The pathophysiology of status epilepticus is reviewed to provide a better understanding of the mechanisms which contribute to status epilepticus, as well as the potential long-term effects. The clinical presentations of different types of status epilepticus in adults are discussed, with emphasis on the hospital course and management of the most dangerous type, generalized convulsive status epilepticus. Strategies for the evaluation and management of status epilepticus are provided based on available evidence from clinical trials and recommendations from the Neurocritical Care Society and the European Federation of Neurological Societies. © 2017 Elsevier B.V. All rights reserved.
Siatouni, Anna; Gatzonis, Stylianos; Alexopoulos, Andreas; Georgakoulias, Nikos; Papathanassiou, Mathildi; Korfias, Stefanos; Zisimopoulou, Vaso; Sakas, Damianos
A 30-year-old woman with intractable seizures evaluated as surgical candidate. During presurgical evaluation an invasive electroencephalogram was recommended to define the location and extent of epileptogenic zone and relationship to epileptogenic lesion. On third monitoring night the patient complained of persistent homonymous hemianopsia following a habitual seizure. Concurrently, persistent epileptic activity was evident in a small, restricted area around the right calcarine fissure. The ictal discharges persisted for the next 30 h despite high-dose administration of intravenous antiepileptic drugs, until patient was taken to operating room. Simple partial status epilepticus presenting with pure visual symptoms is rare and difficult to diagnose, even more so when presenting with negative visual phenomena. Epileptic etiology of unexplained, paroxysmal negative visual symptoms should be considered in the differential diagnosis in patients with pre-existing epilepsy, as well as patients with no prior history of epilepsy. PMID:27162608
D'Giano, C H; Del C García, M; Pomata, H; Rabinowicz, A L
Status epilepticus (SE) represents a medical emergency that annually affects 60,000--150,000 individuals in the United States. Selective neuronal loss in vulnerable areas has been pathologically demonstrated following convulsive SE primarily affecting the limbic system, thalamus and cerebellum. Morbidity in those cases that follow refractory SE (RSE) is poorly documented. There have been anecdotal reports of surgical treatment for this condition, especially secondary to brain lesions. We report a 6-year-old patient who was in RSE for 60 days, without a brain lesion documented by MRI. The patient underwent multiple subpial transection (MST) of the sensorimotor cortex, which by ictal EEG and ictal SPECT proved to be the epileptogenic zone. We conclude that MST should be considered as an alternative treatment for refractory partial SE.
Singh, Sanjay P; Agarwal, Shubhi; Faulkner, M
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. PMID:24791086
Malagón Valdez, Jorge
Status epilepticus is a medical emergency which presents seizures by 30 minutes or more of continuous activity, or two or more consecutive crises without full recovery of consciousness between them. Currently, it is considered that a seizure convulsive or not, that last more than 5 minutes should be considered a status epilepticus. Different drugs for the treatment of this disease have been used. There is a general consensus in an aggressive handling should be done to reduce their morbidity and mortality, without forgetting that the cause of status is important for its management, control, and its aftermath.
Kaufman, Kenneth R; Zuber, Nicole; Rueda-Lara, Maria A; Tobia, Anthony
Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) is a progressive neurodegenerative disorder associated with polygenetic, maternally inherited, mitochondrial DNA mutations. MELAS has multisystem presentation including neurological, muscular, endocrine, auditory, visual, cardiac, psychiatric, renal, gastrointestinal and dermatological symptoms. Clinical course and prognosis are variable, often leading to cognitive decline, disability, and premature death. Both convulsive status epilepticus (CSE) and nonconvulsive status epilepticus (NCSE) are reported with MELAS. This report illustrates a case of MELAS with recurrent complex partial seizures, NCSE, confusion, aggressive behaviors, hallucinations, and paranoid delusions. Rapid video/EEG confirmation of diagnosis and aggressive antiepileptic drug intervention are required. Further education of medical professionals regarding this disorder, its appropriate management, and the significance of NCSE is indicated to avoid delay of treatment. Copyright 2010 Elsevier Inc. All rights reserved.
Abend, Nicholas S.; Bearden, David; Helbig, Ingo; McGuire, Jennifer; Narula, Sona; Panzer, Jessica A.; Topjian, Alexis; Dlugos, Dennis J.
Status epilepticus (SE) describes persistent or recurring seizures without a return to baseline mental status, and is a common neurologic emergency. SE can occur in the context of epilepsy or may be symptomatic of a wide range of underlying etiologies. The clinician’s aim is to rapidly institute care that simultaneously stabilizes the patient medically, identifies and manages any precipitant conditions, and terminates seizures. Seizure management involves “emergent” treatment with benzodiazepines followed by “urgent” therapy with other anti-seizure medications. If seizures persist then refractory SE is diagnosed and management options include additional anti-seizure medications or infusions of midazolam or pentobarbital. This paper reviews the management of pediatric SE and RSE. PMID:25727508
Maganti, Rama; Gerber, Paula; Drees, Cornelia; Chung, Steve
Nonconvulsive status epilepticus (NCSE) is a heterogeneous disorder with multiple subtypes. Although attempts have been made to define and classify this disorder, there is yet no universally accepted definition or classification that encompasses all subtypes or electroclinical scenarios. Developing such a classification scheme is becoming increasingly important, because NCSE is more common than previously thought, with a bimodal peak, in children and the elderly. Recent studies have also shown a high incidence of NCSE in the critically ill. Although strong epidemiological data are lacking, NCSE constitutes about 25-50% of all cases of status epilepticus. For the purposes of this review, we propose an etiological classification for NCSE including NCSE in metabolic disorders, NCSE in coma, NCSE in acute cerebral lesions, and NCSE in those with preexisting epilepsy with or without epileptic encephalopathy. NCSE is still underrecognized, yet potentially fatal if untreated. Diagnosis can be established using an electroencephalogram (EEG) in most cases, sometimes requiring continuous monitoring. However, in comatose patients, diagnosis can be difficult, and the EEG can show a variety of rhythmic or periodic patterns, some of which are of unclear significance. Although some subtypes of NCSE are easily treatable, such as absence status epilepticus, others do not respond well to treatment, and debate exists over how aggressively clinicians should treat NCSE. In particular, the appropriate treatment of NCSE in patients who are critically ill and/or comatose is not well established, and large-scale trials are needed. Overall, further work is needed to better define NCSE, to determine which EEG patterns represent NCSE, and to establish treatment paradigms for different subtypes of NCSE.
Falco-Walter, Jessica J; Bleck, Thomas
Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE.
Falco-Walter, Jessica J.; Bleck, Thomas
Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE. PMID:27120626
Loddenkemper, Tobias; Goodkin, Howard P
Status epilepticus is characterized by a prolonged, self-sustaining seizure or repeated seizures without return to baseline. The clinical manifestations of status epilepticus in children and adults range from overt generalized convulsions to more subtle behavioral manifestations, including unresponsiveness in the setting of the intensive care unit. Status epilepticus is the most common neurologic emergency of childhood. A large proportion of these episodes are the result of a prolonged febrile seizure or an acute symptomatic etiology. Fortunately, status epilepticus occurs without consequence for many children, but for others, it is correlated with long-term neurologic dysfunction or death. Treatment of status epilepticus should commence promptly upon its recognition, using predefined treatment protocols. The goal of treatment is the rapid termination of the seizure, to minimize the acute and chronic effects of this emergency and to allow for the prompt assessment and management of the underlying precipitant. Currently, the drug class of first choice in the in-hospital and out-of-hospital treatment of status epilepticus is the benzodiazepines, which may need to be quickly followed by a next-line agent, as the efficacy of the benzodiazepines is negatively correlated with seizure duration. Traditionally, these next-line agents have included phenobarbital and phenytoin, but emerging evidence supports the use of intravenous formulations of other antiepileptic drugs. If the first two agents fail, high-dose intravenous midazolam or anesthetic therapy should be rapidly initiated. This paper reviews the current treatment options and strategies for pediatric patients with status epilepticus.
Status epilepticus is defined as epileptic seizure with the duration for over 30 min or clustered seizure without complete recovery of consciousness for 30 min or more. From the management point of view, therapeutic intervention is recommended for prolonged seizures for 5 min or more. Intranasal, buccal or intramuscular administration of midazolam is strongly evidence-based and highly recommended method for the treatment of prolonged seizures before the intravenous access. Diazepam or midazolam is the first choice as initial intravenous treatment. Intravenous bolus administration of fosphenytoin or phenobarbital is the second line treatment. General anesthesia using such as thiopental or propofol is indicated for refractory status epileptic, which should be managed in the intensive care unit.
Fernandez, Andres; Claassen, Jan
Refractory status epilepticus (RSE) has a high morbidity and mortality. There are currently no definitive data to guide both the optimal choice of therapy and treatment goals. This review focuses on RSE diagnosis and outcome and discusses both commonly used and anecdotal therapies for RSE. The challenges in performing randomized controlled trials (RCTs) in neurocritical care and more specifically for the treatment of RSE are illustrated by the early termination of the first RCT of RSE due to low recruitment that compared propofol to barbiturates. Recent case series include the successful treatment of recurrent RSE with ketamine, intravenous lacosamide as an add-on treatment, the use of combination antiepileptics (phenytoin, levetiracetam, and pregabalin), and surgical treatments (vagal nerve and deep brain stimulation) for the control of RSE. A number of different therapeutic options are available for the treatment of RSE but none have been shown to be superior to others at this point.
Navarro, V; Fischer, C; Convers, P
The diagnosis of status epilepticus can be retained, wrongly, in several circumstances. Nonepileptic pseudoseizures from a psychiatric origin and some movement disorders can mimic convulsive status epilepticus. Encephalopathy of various causes (post-anoxic, metabolic, toxic, Creutzfeldt-Jakob disease) can be wrongly taken for non-convulsive status epilepticus, mainly due to inadequate interpretation of the electroencephalogram (EEG). In these encephalopathies, the existence of (non-epileptic) myoclonus and the abolition of the EEG abnormalities with the use of a benzodiazepine (without correction of the clinical symptoms) are additional confounding factors, leading to false diagnosis. Nevertheless, in general, the diagnosis of status epilepticus can be confirmed or rejected base on a combined analysis of the clinical data and the EEG.
Smith, Douglas M.; McGinnis, Emily L.; Walleigh, Diana J.; Abend, Nicholas S.
Status epilepticus is a common pediatric neurological emergency. Management includes prompt administration of appropriately selected anti-seizure medications, identification and treatment of seizure precipitant(s), as well as identification and management of associated systemic complications. This review discusses the definitions, classification, epidemiology and management of status epilepticus and refractory status epilepticus in children. PMID:27089373
Pinto, Rovina Fiona; Turnbull, Jennifer
Clinical question Is intravenous (IV) lorazepam superior to IV diazepam in the treatment of pediatric status epilepticus? Article chosen Chamberlain JM, Okada P, Holsti M, et al. Lorazepam v. diazepam for pediatric status epilepticus: a randomized clinical trial. JAMA 2014;311(16):1652-60. To determine whether lorazepam has better efficacy and safety than diazepam for treating pediatric status epilepticus.
Leitinger, M; Kalss, G; Rohracher, A; Pilz, G; Novak, H; Höfler, J; Deak, I; Kuchukhidze, G; Dobesberger, J; Wakonig, A; Trinka, E
Status epilepticus (SE) is a frequent neurological emergency complicated by high mortality and often poor functional outcome in survivors. The aim of this study was to review available clinical scores to predict outcome. Literature review. PubMed Search terms were "score", "outcome", and "status epilepticus" (April 9th 2015). Publications with abstracts available in English, no other language restrictions, or any restrictions concerning investigated patients were included. Two scores were identified: "Status Epilepticus Severity Score--STESS" and "Epidemiology based Mortality score in SE--EMSE". A comprehensive comparison of test parameters concerning performance, options, and limitations was performed. Epidemiology based Mortality score in SE allows detailed individualization of risk factors and is significantly superior to STESS in a retrospective explorative study. In particular, EMSE is very good at detection of good and bad outcome, whereas STESS detecting bad outcome is limited by a ceiling effect and uncertainty of correct cutoff value. Epidemiology based Mortality score in SE can be adapted to different regions in the world and to advances in medicine, as new data emerge. In addition, we designed a reporting standard for status epilepticus to enhance acquisition and communication of outcome relevant data. A data acquisition sheet used from patient admission in emergency room, from the EEG lab to intensive care unit, is provided for optimized data collection. Status Epilepticus Severity Score is easy to perform and predicts bad outcome, but has a low predictive value for good outcomes. Epidemiology based Mortality score in SE is superior to STESS in predicting good or bad outcome but needs marginally more time to perform. Epidemiology based Mortality score in SE may prove very useful for risk stratification in interventional studies and is recommended for individual outcome prediction. Prospective validation in different cohorts is needed for EMSE, whereas
Riviello, James J; Holmes, Gregory L
Status epilepticus (SE) is a life-threatening emergency that requires prompt treatment, including basic neuroresuscitation principles (the ABCs), antiepileptic drugs to stop the seizure, and identification of etiology. Symptomatic SE is more common in younger children. Treating the precipitating cause may prevent ongoing neurologic injury and facilitates seizure control. A systematic treatment regimen, planned in advance, is needed, including one for refractory status epilepticus (RSE). Here we emphasize definitions, clinical and electroencephalography stages, early treatment, special circumstances that may require immediate seizure control, and treatment of RSE. Because much clinical research in SE has been done in adults, we indicate the patient population studied.
Giovannini, Simona; Frattini, Daniele; Scarano, Angela; Fusco, Carlo; Bertani, Gianna; Della Giustina, Elvio; Martinelli, Paola; Orteschi, Daniela; Zollino, Marcella; Neri, Giovanni; Gobbi, Giuseppe
Epilepsy is the most common and serious neurological symptom in ring chromosome 14 syndrome, also characterised by mild dysmorphisms, acquired microcephaly, cognitive impairment, hypotonia and ocular abnormalities. Typically, early-onset, polymorphous and drug-resistant seizures are reported. Status epilepticus has not been previously reported. We describe a nine-year-old Caucasian boy with ring 14 syndrome who presented a severe early-onset and drug-resistant focal epilepsy with secondary generalised seizures and repetitive episodes of convulsive and non-convulsive status epilepticus. The electro-clinical evaluation of prolonged seizures and their long-term consequences is important for the practical management of these patients and for a better comprehension of the syndrome.
Katalin, Tóth; Futó, Judit
Status epilepticus is an emergency situation that can often lead to death or neurocognitive deficits despite adequate therapy is conducted. Etiology and prognosis can be widely heterogeneous. Knowledge of the basic pathophysiologic mechanisms has altered the definition of status epilepticus and the emphasis of therapy has also changed according to that. Today, with neuroprotective approach and recognition of the importance of time-window the management of generalised tonic clonic status became an emergency or critical care task, because intratracheal narcosis is more often and earlier the therapy of choice and even the sufficient treatment can convey serious side effects. In the article, the authors describe the systemic and cerebral pathophysiologic factors during seizure. The authors offer flow-charts illustrating the treatment of patients with generalised tonic clonic status to make the daily work of physicians easier. Early on critical care treatment and multidisciplinary approach is the pledge of reduction in mortality and morbidity.
Nakashima, Kentarou; Ogihara, Masaaki; Kasai-Yoshida, Emi; Tsuruta, Shio; Nakagawa, Machiko; Kusakawa, Isao
We describe a boy (aged 2 years and 7 months) with hemimegalencephaly who developed myoclonic status, which improved dramatically after total callosotomy. The patient experienced seizures beginning at age 2 days, at which time electroencephalography revealed a right unilateral burst suppression pattern, and cranial magnetic resonance imaging revealed an enlarged right hemisphere. At age 8 months, habitual seizures increased to more than daily frequency. At the same time, myoclonic status epilepticus appeared with frequent erratic, partial, massive myoclonic seizures and clouding of consciousness. These signs were accompanied by diffuse spike and spike-wave patterns on electroencephalography, indicating myoclonic status in nonprogressive encephalopathy. Total callosotomy performed at age 10 months resulted in the complete disappearance of myoclonic status and prominent decrease in habitual seizures. This description of hemimegalencephaly is the first, to our knowledge, in which total callosotomy alleviated myoclonic status epilepticus. Although the mechanism of myoclonic status epilepticus remains unknown, our results suggest that cortico-cortical pathways are involved in this type of myoclonic status. Copyright © 2012 Elsevier Inc. All rights reserved.
Lee, Chun-Yu; Yeh, Shin-Joe; Tsai, Li-Kai; Tang, Sung-Chun; Jeng, Jiann-Shing
Status epilepticus was rarely reported as the initial manifestation of intracranial dural arteriovenous fistulas. Successful treatment with endovascular intervention has not been reported in the literature. We report three cases of dural arteriovenous fistulas initially presenting with various types of status epilepticus, including generalized tonic-clonic status epilepticus, complex partial status epilepticus, and nonconvulsive status epilepticus. The status epilepticus of these patients was successfully terminated through aggressive endovascular intervention in conjunction with antiepileptic drugs. These cases highlight the importance of intracranial dural arteriovenous fistulas in diagnosing patients with status epilepticus. Moreover, directly treating dural arteriovenous fistulas plays a crucial role in addition to anti-epileptic drugs therapy in controlling seizures in patients with dural arteriovenous fistulas related status epilepticus.
Opinion Statement Status epilepticus (SE) is a medical emergency consisting of persistent or recurring seizures without a return to baseline mental status. SE is not a single entity, but can be divided into subtypes based on seizure types and underlying etiologies. Management should be implemented rapidly and based on continuously reassessed care pathways. The aim is to terminate seizures while simultaneously identifying and managing precipitant conditions. Seizure management involves “emergent” treatment with benzodiazepines (lorazepam intravenously, midazolam intramuscularly, or diazepam rectally) followed by “urgent” therapy (phenytoin/fosphenytoin, phenobarbital, levetiracetam or valproate sodium). If seizures persist, “refractory” treatments include infusions of midazolam or pentobarbital. Prognosis is dependent on the underlying etiology and seizure persistence. This paper reviews the current management options and strategies for pediatric convulsive status epilepticus. PMID:24909106
Cock, Hannah R
Drug-induced status epilepticus (SE) is a relatively uncommon phenomenon, probably accounting for less than 5% of all SE cases, although limitations in case ascertainment and establishing causation substantially weaken epidemiological estimates. Some antiepileptic drugs, particularly those with sodium channel or GABA(γ-aminobutyric acid)-ergic properties, frequently exacerbate seizures and may lead to SE if used inadvertently in generalized epilepsies or less frequently in other epilepsies. Tiagabine seems to have a particular propensity for triggering nonconvulsive SE sometimes in patients with no prior history of seizures. In therapeutic practice, SE is most commonly seen in association with antibiotics (cephalosporins, quinolones, and some others) and immunotherapies/chemotherapies, the latter often in the context of a reversible encephalopathy syndrome. Status epilepticus following accidental or intentional overdoses, particularly of antidepressants or other psychotropic medications, has also featured prominently in the literature: whilst there are sometimes fatal consequences, this is more commonly because of cardiorespiratory or metabolic complications than as a result of seizure activity. A high index of suspicion is required in identifying those at risk and in recognizing potential clues from the presentation, but even with a careful analysis of patient and drug factors, establishing causation can be difficult. In addition to eliminating the potential trigger, management should be as for SE in any other circumstances, with the exception that phenobarbitone is recommended as a second-line treatment for suspected toxicity-related SE where the risk of cardiovascular complications is higher anyways and may be exacerbated by phenytoin. There are also specific recommendations/antidotes in some situations. The outcome of drug-induced status epilepticus is mostly good when promptly identified and treated, though less so in the context of overdoses. This article is
Bleck, Thomas P
Status epilepticus is treated as a neurologic emergency and only later are the potential etiologies assessed. While sometimes the cause for status epilepticus is apparent (e.g., antiepileptic drug withdrawal), all too often it is not identified, even after extensive diagnostic testing has been performed. With emphasis on the less-common etiologies, this review will cover various probable and known causes of status epilepticus among adults, children, and those patients with refractory epilepsy. PMID:20231917
Liimatainen, Suvi; Ollikainen, Jyrki; Peltola, Jukka
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.
Yokoyama, E; Hirata, Y; Nagata, K
A 45-year-old man developed generalized convulsion and consciousness disturbance at age 43. An X-ray CT revealed hemorrhagic infarction in the left fronto-parieto-temporal area. A conventional angiography disclosed complete occlusion of the left cortical vein. In the chronic stage of the stroke, he had incomplete right quadrantopsia, a mild right hemiparesis and sensory aphasia. The patient has had partial somatosensory seizures since February 1990. Ictal EEG recordings showed epileptogenic discharges in the left parietal region. The seizures were adequately controlled with clonazepam. Since July 27, 1993, he has become aware of blurred vision in both eyes accompanied with headache and dizziness. On August 6, he was admitted to the hospital with right homonymons hemianopsia, sensory aphsia and tonic seizures in the right hand. Ictal EEG recordings demonstrated theta waves of the left parieto-occipital region and epileptogenic discharges in the left occipital region which consisted of spikes, sharp waves and spike-wave complexes. Single photon emission computed tomography (SEPCT) images obtained during seizures showed considerable hyperperfusion in the left occipital temporal lobes, while there was hypoperfusion in the left temporo-parietal area corresponding to the lesion of the old cerebral infarction. A T2-weighted MRI scan showed an abnormal high-intensity area in the left occipital lobe that suggested brain edema. After the admission, the patient was treated with additional anticonvulsant drugs. The tonic seizures in the right hand disappeared and right homonymous hemianopsia and sensory aphasia showed gradual improvement in the next four weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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
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 nonconvulsive status epilepticus remains unknown, this disorder is thought to lead to neuronal damage, so its identification and treatment are important. Nonconvulsive status epilepticus should be considered in the differential diagnosis of patients with liver cirrhosis presenting an altered mental status. We report a case of a 52-year-old male with liver cirrhosis presenting an altered mental status. He was initially diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive status epilepticus by electroencephalogram.
Patterson, Edward Ned E
Status epilepticus (SE) is a medical emergency for companion animals, with significant associated morbidity and mortality. Therapy in companion animals and people has been largely with sedatives and anesthetics, many of which have gamma-aminobutyric acid receptor-mediated mechanisms. Early aggressive treatment includes staged first-line therapy with benzodiazepines, and second- and third-line protocols when needed. Recently, intravenous levetiracetam has also been used in for SE in dogs and people, and there are other human intravenous drug preparations that may hold promise for future use in companion animals.
Bhatnagar, M; Shorvon, S
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
Freilich, Emily R; Schreiber, John M; Zelleke, Tesfaye; Gaillard, William D
Status epilepticus is an acute neurologic emergency, the incidence of which is increasing in the United States as the definition evolves and our detection abilities improve. We will present the current definition of status epilepticus, including a recently modified operational definition for use in the clinical setting. We will also provide updates on identifying children in status epilepticus, etiologic considerations, and the rationale for diagnostic testing. Recent data reveal the benefits of MRI vs. computed tomography in new-onset status epilepticus, as well as high rates of identification of electrographic seizures in patients with unexplained acute encephalopathy in pediatric ICU settings. Genetic testing should be considered in young children with recurrent status epilepticus. Prompt recognition and diagnostic evaluation of the child in status epilepticus will help identify causes, which may require specific treatment, and help in the management of this life-threatening condition. Laboratory work, neuroimaging, electroencephalogram or continuous video electroencephalogram, lumbar puncture, and genetic testing may be considered in the evaluation of the child in status epilepticus.
Grover, Eric H; Nazzal, Yara; Hirsch, Lawrence J
Convulsive status epilepticus (CSE) is a medical emergency with an associated high mortality and morbidity. It is defined as a convulsive seizure lasting more than 5 min or consecutive seizures without recovery of consciousness. Successful management of CSE depends on rapid administration of adequate doses of anti-epileptic drugs (AEDs). The exact choice of AED is less important than rapid treatment and early consideration of reversible etiologies. Current guidelines recommend the use of benzodiazepines (BNZ) as first-line treatment in CSE. Midazolam is effective and safe in the pre-hospital or home setting when administered intramuscularly (best evidence), buccally, or nasally (the latter two possibly faster acting than intramuscular (IM) but with lower levels of evidence). Regular use of home rescue medications such as nasal/buccal midazolam by patients and caregivers for prolonged seizures and seizure clusters may prevent SE, prevent emergency room visits, improve quality of life, and lower health care costs. Traditionally, phenytoin is the preferred second-line agent in treating CSE, but it is limited by hypotension, potential arrhythmias, allergies, drug interactions, and problems from extravasation. Intravenous valproate is an effective and safe alternative to phenytoin. Valproate is loaded intravenously rapidly and more safely than phenytoin, has broad-spectrum efficacy, and fewer acute side effects. Levetiracetam and lacosamide are well tolerated intravenous (IV) AEDs with fewer interactions, allergies, and contraindications, making them potentially attractive as second- or third-line agents in treating CSE. However, data are limited on their efficacy in CSE. Ketamine is probably effective in treating refractory CSE (RCSE), and may warrant earlier use; this requires further study. CSE should be treated aggressively and quickly, with confirmation of treatment success with epileptiform electroencephalographic (EEG), as a transition to non-convulsive status
Stores, G; Zaiwalla, Z; Styles, E; Hoshika, A
The clinical, electrographic and reported neuropsychological features of 50 children with non-convulsive status epilepticus (NCSE) were reviewed and the children's progress followed for one to five years. NCSE occurred in a variety of epilepsies, especially the Lennox-Gastaut syndrome. Clinical manifestations ranged from obvious mental deterioration to subtle changes. The condition had often been overlooked or misinterpreted and many children had experienced repeated episodes over long periods. Following diagnosis, immediate treatment was often not attempted or was not successful. Further episodes of NCSE occurred in the majority of children during the follow up period. Failure to recognise NCSE and to treat episodes promptly, and the high rate of recurrence, is of particular concern in view of fears that repeated exposure to this condition might be brain damaging. At least 28 children in the present series showed evidence of intellectual or educational deterioration over the period during which NCSE had occurred, although the exact cause was difficult to determine. PMID:7574851
Legriel, Stephane; Lemiale, Virginie; Schenck, Maleka; Chelly, Jonathan; Laurent, Virginie; Daviaud, Fabrice; Srairi, Mohamed; Hamdi, Aicha; Geri, Guillaume; Rossignol, Thomas; Hilly-Ginoux, Julia; Boisramé-Helms, Julie; Louart, Benjamin; Malissin, Isabelle; Mongardon, Nicolas; Planquette, Benjamin; Thirion, Marina; Merceron, Sybille; Canet, Emmanuel; Pico, Fernando; Tran-Dinh, Yves-Roger; Bedos, Jean-Pierre; Azoulay, Elie; Resche-Rigon, Matthieu; Cariou, Alain
Background Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus. Methods In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis. The primary outcome was a good functional outcome at 90 days, defined as a Glasgow Outcome Scale (GOS) score of 5 (range, 1 to 5, with 1 representing death and 5 representing no or minimal neurologic deficit). The main secondary outcomes were mortality at 90 days, progression to electroencephalographically (EEG) confirmed status epilepticus, refractory status epilepticus on day 1, "super-refractory" status epilepticus (resistant to general anesthesia), and functional sequelae on day 90. Results A GOS score of 5 occurred in 67 of 138 patients (49%) in the hypothermia group and in 56 of 130 (43%) in the control group (adjusted common odds ratio, 1.22; 95% confidence interval [CI], 0.75 to 1.99; P=0.43). The rate of progression to EEG-confirmed status epilepticus on the first day was lower in the hypothermia group than in the control group (11% vs. 22%; odds ratio, 0.40; 95% CI, 0.20 to 0.79; P=0.009), but there were no significant differences between groups in the other secondary outcomes. Adverse events were more frequent in the hypothermia group than in the control group. Conclusions In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).
Zeiler, F. A.; Matuszczak, M.; Teitelbaum, J.; Gillman, L. M.; Kazina, C. J.
Background. Our goal was to perform a systematic review on the use of repetitive transcranial magnetic stimulation (rTMS) in the treatment of status epilepticus (SE) and refractory status epilepticus (RSE). Methods. MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to August 2015), and gray literature were searched. The strength of evidence was adjudicated using Oxford and GRADE methodology. Results. We identified 11 original articles. Twenty-one patients were described, with 13 adult and 8 pediatric. All studies were retrospective. Seizure reduction/control with rTMS occurred in 15 of the 21 patients (71.4%), with 5 (23.8%) and 10 (47.6%) displaying partial and complete responses, respectively. Seizures recurred after rTMS in 73.3% of the patients who had initially responded. All studies were an Oxford level 4, GRADE D level of evidence. Conclusions. Oxford level 4, GRADE D evidence exists to suggest a potential impact on seizure control with the use of rTMS for FSE and FRSE, though durability of the therapy is short-lived. Routine use of rTMS in this context cannot be recommended at this time. Further prospective study of this intervention is warranted. PMID:26682065
Claudet, Isabelle; Maréchal, Céline
A 2-year-old boy who ingested 0.8-1.5 g of amantadine developed status epilepticus. One hour later, the child presented with agitation, diaphoresis, and vomiting. He was admitted to the pediatric emergency department 2 hours later. Generalized seizures evolved to status epilepticus, with alternating generalized tonic-clonic and partial seizures, over a period of 7 hours. Other initial clinical signs were sinusal tachycardia and reactive bilateral mydriasis. All symptoms resolved within 20 hours, with a good recovery; the child was released from the hospital on day 3.
Zeiler, F A; Zeiler, K J; Teitelbaum, J; Gillman, L M; West, M
Our goal was to perform a systematic review of the literature on the insertion of vagal nerve stimulators (VNS) for refractory status epilepticus (RSE) and its impact on the control of RSE. All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to June 2014), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers (FZ and MW). Overall, 17 studies were identified, with 7 manuscripts and 10 meeting abstracts. A total of 28 patients were treated. In those with generalized RSE, 76% displayed cessation of RSE with VNS insertion. In cases of focal RSE, 25% responded to VNS insertion. Few adverse effects related to VNS insertion were described. We currently cannot recommend the use of VNS for RSE. Oxford level 4, GRADE D evidence exists to suggest improvement in seizure control with the use of urgent VNS in generalized RSE. No comments can be made on the utility of VNS in focal RSE. Further prospective study is warranted. Copyright © 2015 Elsevier B.V. All rights reserved.
Johnson, Mark; Simkins, Thomas
This paper describes the sensor technology and associated electronics of a monitor designed to detect the onset of a seizure disorder called status epilepticus. It is a condition that affects approximately 3-5 percent of those individuals suffering from epilepsy. This form of epilepsy does not follow the typical cycle of start-peak-end. The convulsions continue until medically interrupted and are life threatening. The mortality rate is high without prompt medical treatment at a suitable facility. The paper describes the details of a monitor design that provides an inexpensive solution to the needs of those responsible for the care of individuals afflicted with this disorder. The monitor has been designed as a cooperative research and development effort involving the United States Army Armament Research, Development, and Engineering Center's Benet Laboratories (Benet) and the Cerebral Palsy Center for the Disabled (Center), in association with the Department of Neurology at Albany Medical College (AMC). Benet has delivered a working prototype of the device for field testing, in collaboration with Albany Medical College. The Center has identified several children in need of special monitoring and has agreed to pursue commercialization of the device.
Vargas L, Carmen Paz; Varela E, Ximena; Kleinsteuber S, Karin; Cortés Z, Rocío; Avaria B, María de Los Ángeles
Pediatric Status Epilepticus (SE) is an emergency situation with high morbidity and mortality that requires early and aggressive management. The minimum time criterion to define SE was reduced from 30 to 5 minutes, defined as continuous seizure activity or rapidly recurrent seizures without resumption of consciousness for more than 5 minutes. This definition considers that seizures that persist for > 5 minutes are likely to do so for more than 30 min. Those that persist for more than 30 minutes are more difficult to treat. Refractory SE is the condition that extends beyond 60-120 minutes and requires anesthetic management. Super-refractory SE is the state of no response to anesthetic management or relapse during withdrawal of these drugs. The aim of this review is to provide and update on convulsive SE concepts, pathophysiology, etiology, available antiepileptic treatment and propose a rational management scheme. A literature search of articles published between January 1993 and January 2013, focused on pediatric population was performed. The evidence about management in children is limited, mostly corresponds to case series of patients grouped by diagnosis, mainly adults. These publications show treatment alternatives such as immunotherapy, ketogenic diet, surgery and hypothermia. A 35% mortality, 26% of neurological sequelae and 35% of recovery to baseline condition is described on patients evolution.
Betjemann, John P
Status epilepticus is a heterogeneous disorder with varied definitions and presentations. Taken together, all forms of status epilepticus carry significant morbidity and mortality, much of which is dictated by the underlying etiology. Generalized convulsive status epilepticus, which represents a common form, is a true neurologic emergency that requires emergent management. Treatment focuses on stabilizing the patient and aggressive medical management to achieve the timely termination of seizures. For other forms of status epilepticus including nonconvulsive and focal status epilepticus, the goal remains early seizure termination, but the use of intravenous medications should be weighed against the risks associated with these therapies. The diagnostic evaluation of status epilepticus is guided by the patient's history and should be broad, including a screen for toxins, electrolytes, structural abnormalities, and central nervous system infectious and autoimmune/inflammatory etiologies. Considerable research is still needed to improve our understanding of the mechanisms, consequences, and therapy of status epilepticus. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
A 2-month-old girl survived a lethal serum level of paraldehyde after being given the drug intravenously (IV) for status epilepticus. On the basis of known pharmacokinetic data in man, a slow IV infusion, over a period of five minutes, of 200 mg/kg of paraldehyde followed by a drip of 20 mg/kg/hr should result in safe, rapid control of status epilepticus when first-line anticonvulsant drugs have failed. The paraldehyde should be diluted to a 10% solution with 5% dextrose water.
O'Connor, Sunila E; Ream, Margie A; Richardson, Candy; Mikati, Mohamad A; Trescher, Willam H; Byler, Debra L; Sather, Joan D; Michael, Elizabeth H; Urbanik, Kelly B; Richards, Jennifer L; Davis, Ronald; Zupanc, Mary L; Zupec-Kania, Beth
Refractory status epilepticus carries a high risk of morbidity and mortality for children. Traditional treatment of status epilepticus consists of multiple anticonvulsant drugs and, if needed, induction of a medical coma. The ketogenic diet has been used for intractable epilepsy for many years. The purpose of this article is to report a case series of five patients with refractory status epilepticus successfully managed with the ketogenic diet. A summary of pediatric patients with refractory status epilepticus treated with diet was performed. Ketogenic diet therapy should be considered as a treatment option in pediatric patients with refractory status epilepticus. Copyright © 2014 Elsevier Inc. All rights reserved.
Shein, Steven L.; Reynolds, Thomas Q.; Gedela, Satyanarayana; Kochanek, Patrick M.
Status epilepticus (SE) is a common indication for neurocritical care and can be refractory to standard measures. Refractory SE (RSE) is associated with high morbidity and mortality. Unconventional therapies may be utilized in certain cases, including therapeutic hypothermia (TH), bumetanide, and the ketogenic diet. However, the literature describing the use of such therapies in RSE is limited. Details of a case of TH for RSE in an infant with malignant migrating partial seizures of infancy were obtained from the medical record. A 4-month-old child developed SE that was refractory to treatment with concurrent midazolam, phenobarbital, fosphenytoin, topiramate, levetiracetam, folinic acid, and pyridoxal-5-phosphate. This led to progressive implementation of three unconventional therapies: TH, bumetanide, and the ketogentic diet. Electrographic seizures ceased for the entirety of a 43-hour period of TH with a target rectal temperature of 33.0°C–34.0°C. No adverse effects of hypothermia were noted other than a single episode of asymptomatic hypokalemia. Seizures recurred 10 hours after rewarming was begun and did not abate with reinstitution of hypothermia. No effect was seen with administration of bumetanide. Seizures were controlled long-term within 48 hours of institution of the ketogenic diet. TH and the ketogenic diet may be effective for treating RSE in children. PMID:23667778
Foreman, Brandon P.; Alvarez, Vincent; Cabrera Kang, Christian; Probasco, John C.; Jongeling, Amy C.; Meyers, Emma; Espinera, Alyssa; Haas, Kevin F.; Schmitt, Sarah E.; Gerard, Elizabeth E.; Gofton, Teneille; Kaplan, Peter W.; Lee, Jong W.; Legros, Benjamin; Szaflarski, Jerzy P.; Westover, Brandon M.; LaRoche, Suzette M.; Hirsch, Lawrence J.
Objectives: The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. Methods: Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale). Results: Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes. Conclusions: Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation. PMID:26296517
Rivas-Coppola, Marianna S; Patterson, Amy L; Morgan, Robin; Wheless, James W
Bupropion is a monocyclic antidepressant in the aminoketone class, structurally related to amphetamines. The Food and Drug Administration withdrew this product from the market in 1986 after seizures were reported in bulimic patients. It was later reintroduced in 1989 when the incidence of seizures was shown to be dose-related in the immediate release preparation. Massive bupropion ingestion has been associated with status epilepticus and cardiogenic shock in adults. Seizures have been reported in children, but not status epilepticus. This report highlights a patient who presented with status epilepticus and developed cardiopulmonary arrest after bupropion ingestion. False-positive amphetamine diagnosis from urine drug screen on presentation was reported. We review the presentation, clinical course, diagnostic studies, and outcome of this patient. We then review the literature regarding bupropion overdose in children. Symptoms of bupropion toxicity and risk for seizures are dose-dependent and fatalities have been reported. Our patient developed status epilepticus and cardiopulmonary arrest and then progressed to have a hypoxic ischemic encephalopathy and refractory symptomatic partial seizures. Our report highlights the need to keep this medication away from children in order to prevent accidental overdose. Copyright © 2015 Elsevier Inc. All rights reserved.
Allou, N; Coolen-Allou, N; Delmas, B; Cordier, C; Allyn, J
High-risk pulmonary embolism (PE) is associated with high mortality rate (>50%). In some cases, diagnosis of PE remains a challenge with atypical presentations like in this case report with a PE revealed by status epilepticus. We report the case of a 40-year-old man without prior disease, hospitalized in ICU for status epilepticus. All paraclinical examinations at admission did not show any significant abnormalities (laboratory tests, cardiologic and neurological investigations). On day 1, he presented a sudden circulatory collapse and echocardiography showed right intra-auricular thrombus. He was treated by thrombolysis and arteriovenous extracorporeal membrane oxygenation. After stabilization, computed tomography showed severe bilateral PE. He developed multi-organ failure and died 4days after admission. Pulmonary embolism revealed by status epilepticus has rarely been reported and is associated with poor prognosis. Physicians should be aware and think of the possibility of PE in patients with status epilepticus without any history or risk factors of seizure and normal neurological investigations. Copyright Â© 2016 Elsevier Masson SAS. All rights reserved.
Panwar, Mamta; Usha, Ganapathy; Kumath, Manish
This report describes a 35 year old male who presented with seizures after consuming 4-5 bottles of “ALL-OUT” a commercial composition of pyrethroid used as insecticides. Our case report supports authors reporting an association of pyrethroid poisoning with status epilepticus. PMID:23983421
Hocker, Sara; Prasad, Abhiram; Rabinstein, Alejandro A
We sought to describe the spectrum of cardiac injury in refractory status epilepticus (RSE). We reviewed all patients with RSE between 1999 and 2011 at Mayo Clinic. RSE was defined as generalized convulsive or nonconvulsive status epilepticus (SE) that continued despite initial therapies. Exclusion criteria were age <18 years, anoxic SE, psychogenic SE, simple partial SE, absence SE, and repeat RSE. Patients were divided into those with (transient left ventricular [LV] dysfunction; electrocardiography [ECG] abnormality-new T-wave inversion, ST elevation or ST depression, or QTc prolongation; and/or elevated blood troponin T levels) versus those without evidence of cardiac injury. We identified 59 consecutive patients with RSE. In 24 patients no cardiac-specific diagnostic studies were obtained. Twenty-two of the remaining 35 patients demonstrated markers of cardiac injury. General anesthesia was necessary for control of seizures in 31 of 35 patients for 10.5 ± 17.4 days. Twenty-three patients had troponin levels drawn at onset of SE, of which nine were abnormal. ECG findings at onset of SE included ST elevation (11.4%), ST depression (5.7%), new T-wave inversion (37.1%), and nonspecific ST changes (37.1%). Cardiac arrhythmias included ventricular tachycardia/fibrillation (11.4%), atrioventricular block (2.9%), atrial fibrillation/flutter (20.0%), sinus bradycardia (48.6%), and sinus tachycardia (65.7%). Intervention was required for cardiac arrhythmias in 42.9%. QTc was prolonged in 22.9% of patients. One patient met criteria for non-ST-elevation myocardial infarction (NSTEMI). Three of 14 patients evaluated with ECG during SE demonstrated reversible systolic dysfunction. In-hospital mortality was 34.3%. Outcome was worse in the group with markers of cardiac injury but the difference was not statistically significant (p = 0.14). Markers of cardiac injury are common in RSE and may be underrecognized in this population. These disturbances may require specific
Fernández-Torre, José Luis
Nonconvulsive status epilepticus (SE) is a term used to denote a range of conditions in which electrographic seizure activity is prolonged and results in nonconvulsive clinical symptoms. Nowadays, some experts on nonconvulsive SE have emphasized the utility on the clinical practice to consider the classification taking in account both the clinical setting and the severity of consciousness impairment, differentiating between ambulatory patients (from almost normal mental state to stupor) which includes absence SE and complex partial SE; and nonconvulsive SE in coma. To review the literature in relation to the diagnosis of nonconvulsive SE in comatose and/or critically ill patients. Nonconvulsive SE has been reported with surprising frequency in a wide variety of acute neurological processes such as cerebrovascular disease, anoxia, subarachnoid hemorrhage, cranial trauma, encephalitis and following convulsive SE. Nonconvulsive seizures and episodes of nonconvulsive SE in patients with severe impairment of consciousness are frequent and, therefore, continuous EEG monitoring is an essential neurophysiologic tool in the evaluation of comatose subjects. EEG interpretation in patients with nonconvulsive SE may be particularly difficult and problematic and, therefore, requires expert knowledge and a clinical and neurophysiologic specific training.
Starreveld, E.; Starreveld, A. A.
OBJECTIVE: To inform primary care physicians about current issues around generalized convulsive status epilepticus (GCSE) emphasizing definition, pathophysiology, treatment, and prognosis. QUALITY OF EVIDENCE: MEDLINE (1994 to 1999) provided 479 references using the MeSH terms "status epilepticus" and "treatment." From these we selected 30 English-language articles covering clinical aspects, treatment, and animal research. Key source documents from previous years and information from modern textbooks and recent symposia were also included. MAIN MESSAGE: Generalized convulsive status epilepticus continues to be a medical emergency with high morbidity and mortality. It must be managed promptly and effectively. The operational definition of GCSE is a seizure that lasts longer than 5 minutes or two or more seizures between which patients do not recover. Main differential diagnosis is nonepileptic status. Intravenous therapy with combined lorazepam and phenytoin is the initial treatment of choice. Other preferred medications are diazepam, midazolam, and propofol. Some of these medications should be considered before arrival at hospital. Prognosis of GCSE is determined by underlying cause, delay in adequate treatment, and comorbidity. Patients with GCSE lasting longer than 30 minutes require intensive care and electroencephalogram monitoring. CONCLUSION: Intravenous lorazepam and phenytoin are currently the most effective drugs for initial management of GCSE. Timely administration of antiepileptic medication can prevent development of GCSE in some patients with known epilepsy. Main differential diagnosis is nonepileptic status. PMID:11013800
Hwang, Woo Sub; Gwak, Hye Min; Seo, Dae-Won
Propofol is used for treating refractory status epilepticus, which has high rate of mortality. Propofol infusion syndrome is a rare but often fatal syndrome, characterized by lactic acidosis, lipidemia, and cardiac failure, associated with propofol infusion over prolonged periods of time. We investigated the clinical factors that characterize propofol infusion syndrome to know the risk of them in refractory status epilepticus. This retrospective observation study was conducted in Samsung medical center from Jan. 2005 to Dec. 2009. Thirty two patients (19 males, 13 females, aged between 16 and 64 years), with refractory status epilepsy were included. Their clinical findings and treatment outcomes were evaluated retrospectively. We divided our patients into established status epilepticus (ESE) and refractory status epilepticus (RSE). And then the patients with RSE was further subdivided into propofol treatment group (RSE-P) and the other anesthetics treatment group (RSE-O). We analyzed the clinical characteristics by comparison of the groups. There were significant differences of hypotension and lipid change between ESE and RSE (p<0.05). However, there was no significant difference between RSE-P and RSE-O groups. The hospital days were longer in RSE than in ESE (p=0.012) and treatment outcome was also worse in RSE than in ESE (p=0.007) but there were no significant differences of hospital stays and treatment outcome between RSE-P and RSE-O. RSE is very critical disease with high mortality, which may show as many clinical changes as propofol infusion syndrome. Therefore propofol infusion syndrome might be considered as one of the clinical manifestations of RSE.
Hwang, Woo Sub; Gwak, Hye Min; Seo, Dae-Won
Background and Purpose: Propofol is used for treating refractory status epilepticus, which has high rate of mortality. Propofol infusion syndrome is a rare but often fatal syndrome, characterized by lactic acidosis, lipidemia, and cardiac failure, associated with propofol infusion over prolonged periods of time. We investigated the clinical factors that characterize propofol infusion syndrome to know the risk of them in refractory status epilepticus. Methods: This retrospective observation study was conducted in Samsung medical center from Jan. 2005 to Dec. 2009. Thirty two patients (19 males, 13 females, aged between 16 and 64 years), with refractory status epilepsy were included. Their clinical findings and treatment outcomes were evaluated retrospectively. We divided our patients into established status epilepticus (ESE) and refractory status epilepticus (RSE). And then the patients with RSE was further subdivided into propofol treatment group (RSE-P) and the other anesthetics treatment group (RSE-O). We analyzed the clinical characteristics by comparison of the groups. Results: There were significant differences of hypotension and lipid change between ESE and RSE (p<0.05). However, there was no significant difference between RSE-P and RSE-O groups. The hospital days were longer in RSE than in ESE (p=0.012) and treatment outcome was also worse in RSE than in ESE (p=0.007) but there were no significant differences of hospital stays and treatment outcome between RSE-P and RSE-O. Conclusions: RSE is very critical disease with high mortality, which may show as many clinical changes as propofol infusion syndrome. Therefore propofol infusion syndrome might be considered as one of the clinical manifestations of RSE. PMID:24649467
Abend, Nicholas S; Dlugos, Dennis J
We aimed to describe nonconvulsive status epilepticus in terms of patient age, etiology, initial presentation, and electroencephalogram and neuroimaging findings. Twenty children with nonconvulsive status epilepticus were identified by a retrospective review of children who underwent long-term electroencephalogram monitoring in a pediatric intensive care unit. Age ranged from 2 months to 18 years, and in 30% of patients, the age was <1 year. Nonconvulsive status epilepticus occurred most commonly in children with prior epilepsy (35%) or congenital heart disease (25%). Prior to nonconvulsive status epilepticus, most had experienced isolated seizures (55%) or convulsive status epilepticus (20%), but some had only preceding mental-status change (25%). The most common etiologies were exacerbation of epilepsy (35%) and ischemic stroke (25%). No children aged <1 year had preexisting epilepsy. Electroencephalograms confirmed nonconvulsive status epilepticus immediately in 65%. Nonconvulsive status epilepticus lasted up to 8 days, and neuroimaging was abnormal in 82% of patients. Nonconvulsive status epilepticus occurs in a heterogeneous group of children, results from acute symptomatic etiologies in children aged <1 year, most frequently follows isolated convulsions but can occur with only preceding mental status change, and is often prolonged. These findings suggest that a high level of suspicion for nonconvulsive status epilepticus must be maintained, and long-term electroencephalogram monitoring may be indicated in a large number of patients.
Barrueto, Fermin; Green, Jonah; Howland, Mary Ann; Hoffman, Robert S; Nelson, Lewis S
A 34-year-old male with lumbar disc disease and surgery was placed on gabapentin daily for chronic back pain. He remained on a steady dose of 8000 mg/day for 9 months, almost doubled what is considered therapeutic. He ran out of medication, was unable to refill his prescription for 2 days and presented to the emergency department in status epilepticus. There was no previous history of seizure disorder and he was on no other medications. A medical evaluation for an alternative etiology of his seizures was negative. Although gabapentin withdrawal has been previously reported and usually consists of anxiety, diaphoresis, and palpitations, this is the first reported patient with generalized seizures and status epilepticus secondary to gabapentin withdrawal.
Holmes, G L; Riviello, J J
Status epilepticus, a serious, life-threatening emergency characterized by prolonged seizure activity, occurs most commonly in pediatric patients. Although initial therapies with agents such as diazepam, phenytoin, or phenobarbital generally terminate seizure activity within 30-60 minutes, patients with refractory status epilepticus (RSE) lasting longer require additional intervention. High-dose pentobarbital has been the most commonly prescribed agent for the management of RSE in children; however, midazolam has emerged as a new treatment option. This review compares the use of midazolam with pentobarbital in published reports of pediatric RSE. Both drugs effectively terminated refractory seizure activity, although pentobarbital use was complicated by hypotension, delayed recovery, pneumonia, and other adverse effects. Midazolam use was effective and well tolerated, affirming its value in pediatric RSE management.
Alving, Jørgen; Beniczky, Sándor
The aim of this study was to assess how frequently prodromes occur in an adult patient group from a tertiary referral epilepsy centre and to investigate the EEG changes during the prodromes. 578 consecutive patients were interviewed on subjective phenomena, experiences heralding the seizures, for at least 30min before the start of the seizure. EEGs were recorded during the prodromes. Ten out of 490 included patients had prodromes (2%). We were able to record EEG during prodromes in 6 patients. Three patients had EEG changes corresponding to nonconvulsive status epilepticus. Three patients had unrevealing EEG recordings during prodromes. Our results suggest that at least in a part of the patients, the prodromes are actually ictal phenomena, and should be treated as nonconvulsive status epilepticus. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Curless, R G; Holzman, B H; Ramsay, R E
Intravenous (IV) diazepam or phenobarbital is generally accepted as the initial treatment of choice for status epilepticus in children. The risk of severe respiratory depression with either drug is a major problem, particularly in emergency centers that do not have appropriate equipment or personnel for rapid endotracheal intubation of infants. While some pediatric centers are not reluctant to recommend paraldehyde for secondary therapy in status epilepticus, most texts and publications recommend it only as a last resort because of reported complications. We investigated the benefits and complications from varied dosing regimens in 16 trials. The results indicated no significant complications in patients who did not receive an initial IV bolus. Even though treatment with phenobarbital or diazepam and phenytoin sodium had failed, 37% had a good therapeutic response.
Primavera, Alberto; Cocito, Leonardo; Audenino, Daniela
Cephalosporins may induce nonconvulsive status epilepticus (NCSE), a potentially reversible condition. Despite the wide use of these antibiotics, there are only few reported cases, because this condition is probably underestimated. We report two new cases of NCSE occurring during treatment with cefepime and ceftazidime, and emphasize the utility of emergent electroencephalogram in patients with an acute altered state of consciousness while receiving treatment with cephalosporins, particularly when there is evidence of impaired renal function.
Safe, A. F.; Griffiths, K. D.; Maxwell, R. T.
A 30 year old male patient with thyrotoxic crisis presenting as status epilepticus is reported. The aetiology, manifestations and management of this medical emergency are discussed. The importance of prompt, vigorous and comprehensive treatment of thyrotoxic crisis is emphasized. Rapid control of hyperthyroidism as well as other supportive measures are essential if the high fatality rate is to be reduced. Comprehensive management reduces mortality from 90% to 20%. PMID:2349191
Al-Khamees, Wafa'a A; Schwartz, Michael D; Alrashdi, Saleh; Algren, Adam D; Morgan, Brent W
The use of herbal and complementary medicine is common. Many herbal products are known to produce serious adverse effects. Borage oil is derived from the seeds of the borage plant (Borago officinalis) an abundant source of gamma-linolenic acid (GLA), and Borage oil has been promoted as a treatment for rheumatoid arthritis, atopic dermatitis, diabetic neuropathy, and menopause-related symptoms. We report a case of status epilepticus in a patient who consumed borage oil for one week.
Legriel, Stephane; Brophy, Gretchen M.
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
Broomall, Eileen; Natale, JoAnne E.; Grimason, Michele; Goldstein, Joshua; Smith, Craig M.; Chang, Celia; Kanes, Stephen; Rogawski, Michael A.; Wainwright, Mark S.
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
Millikan, Dan; Rice, Brian; Silbergleit, Robert
Current thinking about the acute treatment of status epilepticus (SE) emphasizes a more aggressive clinical approach to this common life-threatening neurologic emergency. In this review, the authors consider four concepts that can accelerate effective treatment of SE. These include (1) updating the definition of SE to make it more clinically relevant, (2) consideration of faster ways to initiate first-line benzodiazepine therapy in the prehospital environment, (3) moving to second-line agents more quickly in refractory status in the emergency department, and (4) increasing detection and treatment of unrecognized nonconvulsive SE in comatose neurologic emergency patients.
Mishra, Devendra; Sharma, Suvasini; Sankhyan, Naveen; Konanki, Ramesh; Kamate, Mahesh; Kanhere, Sujata; Aneja, Satinder
Status epilepticus has a wide etiological spectrum, and significant morbidity and mortality. Management using a pre-determined uniform protocol leads to better outcomes. Multiple protocols for management of childhood status epilepticus are available, without much consensus. A 'Multi-disciplinary Consensus Development Workshop on Management of Status Epilepticus in Children in India' was organized. The invited experts included Pediatricians, Pediatric neurologists, Neurologists, Epileptologists, and Pediatric intensive care specialists from India, with experience in the relevant field. Experts had previously been divided into focus groups and had interacted on telephone and e-mail regarding their group recommendations, and developed consensus on the topic. During the meeting, each group presented their recommendations, which were deliberated upon by the house and a consensus was reached on various issues; the document was finalized after incorporating suggestions of experts on the draft document. To provide consensus guidelines on evaluation and management of convulsive status epilepticus in children in India (excluding neonatal and super-refractory status epilepticus). Each institution should use a pre-determined protocol for management of status epilepticus; pre-hospital management and early stabilization is the key to a satisfactory outcome of status epilepticus. Pharmacotherapy should not be delayed for any investigations; the initial management should consist of a parenteral benzodiazepine by any route feasible. Subsequent management has been detailed. The group also felt the need for more epidemiological research on status epilepticus from India, and identified certain research areas for the purpose.
Sutter, Raoul; Kaplan, Peter W
Status epilepticus refractory to first-line and second-line antiepileptic treatments challenges neurologists and intensivists as mortality increases with treatment refractoriness and seizure duration. International guidelines advocate anesthetic drugs, such as continuously administered high-dose midazolam, propofol, and barbiturates, for the induction of therapeutic coma in patients with treatment-refractory status epilepticus. The seizure-suppressing effect of anesthetic drugs is believed to be so strong that some experts recommend using them after benzodiazepines have failed. Although the rationale for the use of anesthetic drugs in patients with treatment-refractory status epilepticus seems clear, the recommendation of their use in treating status epilepticus is based on expert opinions rather than on strong evidence. Randomized trials in this context are lacking, and recent studies provide disturbing results, as the administration of anesthetics was associated with poor outcome independent of possible confounders. This calls for caution in the straightforward use of anesthetics in treating status epilepticus. However, there are still more questions than answers, and current evidence for the adverse effects of anesthetic drugs in patients with status epilepticus remains too limited to advocate a change of treatment algorithms. In this overview, the rationale and the conflicting clinical implications of anesthetic drugs in patients with treatment-refractory status epilepticus are discussed, and remaining questions are elaborated. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.
Bauerschmidt, Andrew; Martin, Andrew; Claassen, Jan
Status epilepticus has a high morbidity and mortality. There are little definitive data to guide management; however, new recent data continue to improve understanding of management options of status epilepticus. This review examines recent advancements regarding the critical care management of status epilepticus. Recent studies support the initial treatment of status epilepticus with early and aggressive benzodiazepine dosing. There remains a lack of prospective randomized controlled trials comparing different treatment regimens. Recent data support further study of intravenous lacosamide as an urgent-control therapy, and ketamine and clobazam for refractory status epilepticus. Recent data support the use of continuous EEG to help guide treatment for all patients with refractory status epilepticus and to better understand epileptic activity that falls on the ictal-interictal continuum. Recent data also improve our understanding of the relationship between periodic epileptic activity and brain injury. Many treatments are available for status epilepticus and there are much new data guiding the use of specific agents. However, there continues to be a lack of prospective data supporting specific regimens, particularly in cases of refractory status epilepticus.
Goonawardena, Janindu; Marshman, Laurence A G; Drummond, Katharine J
We have reviewed the scant literature on status epilepticus in patients with brain tumours. Patients with brain tumour-associated epilepsy (TAE) appear less likely to develop status epilepticus (TASE) than patients with epilepsy in the general population (EGP) are to develop status epilepticus (SEGP). TASE is associated with lesions in similar locations as TAE; in particular, the frontal lobes. However, in contrast to TAE, where seizures commence early in the course of the disease or at presentation, TASE is more likely to occur later in the disease course and herald tumour progression. In marked contrast to TAE, where epilepsy risk is inversely proportional to Word Health Organization tumour grade, TASE risk appears to be directly proportional to tumour grade (high grade gliomas appear singularly predisposed). Whilst anti-epileptic drug (AED) resistance is more common in TAE than EGP (with resistance directly proportional to tumour grade and frontal location), TASE appears paradoxically more responsive to simple AED regimes than either TAE or SEGP. Although some results suggest that mortality may be higher with TASE than with SEGP, it is likely that (as with SEGP) the major determinant of mortality is the underlying disease process. Because all such data have been derived from retrospective studies, because TASE and SEGP are less common than TAE and EGP, and because TASE and SEGP classification has often been inconsistent, findings can only be considered preliminary: multi-centre, prospective studies are required. Whilst preliminary, our review suggests that TASE has a distinct clinical profile compared to TAE and SEGP. Copyright © 2014 Elsevier Ltd. All rights reserved.
Monti, Giulia; Tondelli, Manuela; Giovannini, Giada; Bedin, Roberta; Nichelli, Paolo F; Trenti, Tommaso; Meletti, Stefano; Chiari, Annalisa
Tau protein is a phosphorylated microtubule-associated protein, principally localized at neuronal level in the central nervous system (CNS). Tau levels in the cerebrospinal fluid (CSF) are considered to index both axonal and neuronal damage. To date, however, no study has specifically evaluated the CSF levels of tau proteins in patients with status epilepticus (SE). We evaluated these established biomarkers of neuronal damage in patients with SE who received a lumbar puncture during SE between 2007 and 2014. Status epilepticus cases due to acute structural brain damage, including CNS infection, were excluded. Clinical, biological, therapeutic, and follow-up data were collected. Group comparison between patients stratified according to SE response to antiepileptic drugs (AEDs), disability, and epilepsy outcomes were performed. Twenty-eight patients were considered for the analyses (mean age 56 years): 14 patients had abnormally high CSF t-tau level, six patients had abnormally high CSF p-tau level, and only three patients had abnormally low Aβ1-42 level. Cerebrospinal fluid t-tau value was higher in patients who developed a refractory SE compared to patients with seizures controlled by AED. Cerebrospinal fluid t-tau values were positively correlated with SE duration and were higher in patients treated with propofol anesthesia compared to patients that had not received this treatment. Patients with higher CSF t-tau had higher risk of developing disability (OR = 32.5, p = 0.004) and chronic epilepsy (OR = 12; p = 0.016) in comparison with patients with lower CSF t-tau level. Our results suggest that CSF t-tau level might be proposed as a biomarker of SE severity and prognosis. Prospective studies are needed to evaluate the effects of propofol on tau pathology in this setting. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.
Jaraba, Sonia; Puig, Oriol; Miró, Júlia; Velasco, Roser; Castañer, Sara; Rodríguez, Laura; Izquierdo, Cristina; Simó, Marta; Veciana, Misericordia; Falip, Mercè
Stroke-like migraine attacks after radiation therapy (SMART) is a late-onset complication of brain irradiation of unknown physiopathology. Our aim was to present three patients with SMART syndrome who had clinical and neuroimage studies suggestive of status epilepticus. Patient 1. A 69-year-old woman, who was treated with radiation therapy 14 years before her first admission to the Neurology Department, presented with several episodes of headache, speech disturbances, and weakness of left limbs with altered awareness. Patient 2. A 49-year-old man, who was treated with whole brain radiation 20 years before the onset of symptoms, developed some episodes consisting of headache and numbness of the right side of face and right arm; the latest episodes were accompanied by visual disturbances followed by generalized tonic-clonic seizures. Patient 3. A 40-year-old man, who received cranial irradiation 20 years before, suffered three episodes of behavioral disturbance, aphasia, headache, and visual aura followed by left homonymous hemianopia. All three patients suffered seizures mostly with visual aura. Electroencephalography showed interictal epileptiform discharges or focal slowing. Brain magnetic resonance image (MRI), positron emission tomography (PET), or ictal-single-photon emission computed tomography (SPECT) showed focal cortical hyperperfusion. Focal diffusion restriction and focal gadolinium-enhancement were observed on MRI. All patients were treated with antiepileptic drugs, being effective in one of them. One patient needed anesthesic coma, and the other patient responded to therapy with corticosteroids. Taking into account clinical evolution and ictal neuroimaging studies, status epilepticus could explain the origin of these episodes in SMART syndrome. Although most patients have reversible symptoms, in some cases, aggressive treatment to avoid sequelae is needed. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier
Anastogiannis, Haralabos; Karanasios, Panagiotis; Makridou, Alexandra; Makris, Nicolaos; Argyriou, Andreas A
Cobalamin deficiency is included in the spectrum of very uncommon underlying causes of status epilepticus (SE) and the literature contains very few such cases. We herein report a case of unusual presentation of cobalamin (vitamin B12) deficiency with de novo SE with the intention to bolster the argument that a de novo manifestation of SE due to cobalamin deficiency might not be that uncommon. We also support the importance of prompt identification and treatment of the underlying causes of SE, particularly those which are uncommon.
Appavu, Brian; Vanatta, Lisa; Condie, John; Kerrigan, John F; Jarrar, Randa
We aimed to study whether ketogenic diet (KD) therapy leads to resolution of super-refractory status epilepticus in pediatric patients without significant harm. A retrospective review was performed at Phoenix Children's Hospital on patients with super-refractory status epilepticus undergoing ketogenic diet therapy from 2011 to 2015. Ten children with super-refractory status epilepticus, ages 2-16 years, were identified. 4/10 patients had immune mediated encephalitis, including Rasmussen encephalitis, anti-N-methyl-d-aspartate receptor encephalitis, and post-infectious mycoplasma encephalitis. Other etiologies included Lennox Gastaut Syndrome, non-ketotic hyperglycinemia, PCDH19 and GABRG2 genetic epilepsy, New Onset Refractory Status Epilepticus, and Febrile Infection-Related Epilepsy Syndrome. 4/10 patients' EEG features suggested focal with status epilepticus, and 6/10 suggested generalized with status epilepticus. Median hospital length was 61days and median ICU length was 27days. The median number of antiepileptic medications prior to diet initiation was 3.0 drugs, and the median after ketogenic diet treatment was 3.5 drugs. Median duration of status epilepticus prior to KD was 18days. 9/10 patients had resolution of super-refractory status epilepticus in a median of 7days after diet initiation. 8/9 patients were weaned off anesthesia within 15days of diet initiation, and within 1day of achieving ketonuria. 1/10 patients experienced side effects on the diet requiring supplementation. Most patients achieved resolution of status epilepticus on KD therapy, suggesting it could be an effective therapy that can be utilized early in the treatment of children with super refractory status epilepticus. Copyright © 2016. Published by Elsevier Ltd.
Novy, Jan; Logroscino, Giancarlo; Rossetti, Andrea O
Status epilepticus (SE) that is resistant to two antiepileptic compounds is defined as refractory status epilepticus (RSE). In the few available retrospective studies, estimated RSE frequency is between 31% and 43% of patients presenting an SE episode; almost all seem to require a coma induction for treatment. We prospectively assessed RSE frequency, clinical predictors, and outcome in a tertiary clinical setting. Over 2 years we collected 128 consecutive SE episodes (118 patients) in adults. Clinical data and their relationship to outcome (mortality and return to baseline clinical conditions) were analyzed. Twenty-nine of 128 SE episodes (22.6%) were refractory to first- and second-line antiepileptic treatments. Severity of consciousness impairment and de novo episodes were independent predictors of RSE. RSE showed a worse outcome than non-RSE (39% vs. 11% for mortality; 21% vs. 63% for return to baseline clinical conditions). Only 12 patients with RSE (41%) required coma induction for treatment. This prospective study identifies clinical factors predicting the onset of SE refractoriness. RSE appears to be less frequent than previously reported in retrospective studies; furthermore, most RSE episodes were treated outside the intensive care unit (ICU). Nonetheless, we confirm that RSE is characterized by high mortality and morbidity.
Rossetti, Andrea O.; Lowenstein, Daniel H.
Summary Refractory status epilepticus (RSE) can be defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. RSE should be treated promptly to prevent morbidity and mortality; however, scarce evidence is available to support the choice of specific treatments. Major independent outcome predictors are age (not modifiable) and etiology (that should be actively targeted). Recent recommendations for adults, relying upon limited evidence, suggest that RSE treatment aggressiveness should be tailored to the clinical situation: to minimize ICU-related complications, focal RSE without major consciousness impairment might initially be approached more conservatively; conversely, early induction of pharmacological coma is advisable in generalized-convulsive forms. At this stage, midazolam, propofol or barbiturates represent the most used alternatives. Several other treatments, such as additional anesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (electroconvulsive treatment, hypothermia), have been used in protracted RSE. Treatment lasting weeks or months may sometimes result in a good outcome, as in selected cases after cerebral anoxia and encephalitis. Well-designed prospective studies of this condition are urgently needed. PMID:21939901
Zeiler, Frederick A; Zeiler, Kaitlin J; Teitelbaum, Jeanne; Gillman, Lawrence M; West, Michael; Kazina, Colin J
Our goal was to perform a systematic review of the literature on the use of intravenous lidocaine in pediatrics for status epilepticus (SE) and refractory status epilepticus (RSE) to determine its impact on seizure control. All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to November 2014), and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and Grading of Recommendations Assessment, Development, and Evaluation methodologies by two independent reviewers. Overall, 20 original studies were identified, with 19 manuscripts and one meeting abstract. Two hundred and thirty-five pediatric patients were treated for 252 episodes of SE/RSE. Patients had varying numbers of antiepileptic drugs (two to eight) on board before lidocaine therapy. During 20 of the 252 (7.9%) episodes of SE/RSE, phenytoin was on board. The dose regimen of lidocaine varied, with some using bolus dosing alone; others used a combination of bolus and infusion therapy. Overall, 60.0% of seizures responded to lidocaine, with complete cessation and greater than 50% reduction seen in 57.6% and 12.3%, respectively. Patient outcomes were sparingly reported. There currently exists Oxford level 2b, Grading of Recommendations Assessment Development, and Evaluation C evidence to support the consideration of lidocaine for SE and RSE in the pediatric population. Further prospective studies of lidocaine administration in this setting are warranted.
Flügel, Dominique; Kim, Olaf Chan-Hi; Felbecker, Ansgar; Tettenborn, Barbara
Sudden onset of aphasia is usually due to stroke. Rapid diagnostic workup is necessary if reperfusion therapy is considered. Ictal aphasia is a rare condition but has to be excluded. Perfusion imaging may differentiate acute ischemia from other causes. In dubious cases, EEG is required but is time-consuming and laborious. We report a case where we considered de novo status epilepticus as a cause of aphasia without any lesion even at follow-up. A 62-year-old right-handed woman presented to the emergency department after nurses found her aphasic. She had undergone operative treatment of varicosis 3 days earlier. Apart from hypertension and obesity, no cardiovascular risk factors and no intake of medication other than paracetamol were reported. Neurological examination revealed global aphasia and right pronation in the upper extremity position test. Computed tomography with angiography and perfusion showed no abnormalities. Electroencephalogram performed after the CT scan showed left-sided slowing with high-voltage rhythmic 2/s delta waves but no clear ictal pattern. Intravenous lorazepam did improve EEG slightly, while aphasia did not change. Lumbar puncture was performed which likely excluded encephalitis. Magnetic resonance imaging showed cortical pathological diffusion imaging (restriction) and cortical hyperperfusion in the left parietal region. Intravenous anticonvulsant therapy under continuous EEG resolved neurological symptoms. The patient was kept on anticonvulsant therapy. Magnetic resonance imaging after 6 months showed no abnormalities along with no clinical abnormalities. Magnetic resonance imaging findings were only subtle, and EEG was without clear ictal pattern, so the diagnosis of aphasic status remains with some uncertainty. However, status epilepticus can mimic stroke symptoms and has to be considered in patients with aphasia even when no previous stroke or structural lesions are detectable and EEG shows no epileptic discharges. Epileptic origin is
Prasad, A N
Status epilepticus in the pediatric intensive care setting is a neurological emergency. Its management presents profound challenges for the pediatric intensivist, and neurologist. Understanding the neurobiological factors that are operative in transition of an epileptic seizure to self-sustained status epilepticus is critical to management. Statue epilepticus in children is often heterogeneous in etiology. In this article, I examine the evidence for who is likely to be admitted to the pediatric intensive care unit for management, the risk factors, the relationship of seizure duration and evolution to status epilepticus, and the reasons for seizure refractoriness. The immediate complications and long term consequences leading to morbidity and mortality in this condition are reviewed. The problem of refractory status epilepticus is particularly more frequently encountered in the intensive care setting. Therapeutic options in the initial management and in particular addressing reasons for the development of pharmacoresistance in status epilepticus are presented. Finally, data on outcome in the pediatric ICU setting is discussed providing thus an overview of our current understanding and state of the art in the management of status epilepticus in children.
Teran, Felipe; Harper-Kirksey, Katrina; Jagoda, Andy
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.
Hoskote, Sumedh S; Annapureddy, Narender; Ramesh, Atul K; Rose, Keith; Jones, James P
We present the case of a 52-year-old man with hypertension, diastolic congestive heart failure, end-stage renal disease on hemodialysis 3 times a week and a remote history of a hemorrhagic stroke who presented to the emergency department with a vesicular rash on his left arm. The rash was observed to be in a dermatomal distribution, and a diagnosis of herpes zoster was made. The patient was discharged home on valacyclovir 1 g 3 times a day for a duration of 7 days. The patient took 2 doses of valacyclovir before presenting to the hospital again with irritability and hallucinations. Over the next several days, the patient's neurologic status declined and he became disoriented and increasingly somnolent. Because of a concern for varicella zoster virus (VZV) or herpes simplex virus (HSV) meningoencephalitis, acyclovir was initiated intravenously at 600 mg (10 mg/kg) for every 12 hours. Computed tomography and magnetic resonance imaging of the brain failed to reveal an acute process. Electroencephalogram was interpreted as seizure activity versus metabolic encephalopathy. Lumbar puncture was not suggestive for meningitis, subarachnoid hemorrhage, or HSV/VZV infection. The patient subsequently had a witnessed seizure during dialysis and was felt to have status epilepticus due to acyclovir and valacyclovir neurotoxicity. The patient underwent daily hemodialysis for removal of the drug and eventually made a full neurologic recovery. Our case highlights that acyclovir neurotoxicity can result in status epilepticus, hallucinations, and altered consciousness. Differentiating acyclovir neurotoxicity from HSV or VZV meningoencephalitis is of crucial importance because the symptoms are similar but the management is vastly different.
Sánchez, Sebastián; Rincon, Fred
Status epilepticus (SE) is defined as a continuous clinical and/or electrographic seizure activity lasting five minutes or more or recurrent seizure activity without return to baseline. There is a paucity of epidemiological studies of SE, as most research is derived from small population studies. The overall incidence of SE is 9.9 to 41 per 100,000/year, with peaks in children and the elderly and with febrile seizures and strokes as its main etiologies. The etiology is the major determinant of mortality. Governments and the academic community should predominantly focus on the primary prevention of etiologies linked to SE, as these are the most important risk factors for its development. This review describes the incidence, prevalence, etiology, risk factors, outcomes and costs of SE and aims to identify future research and public health needs. PMID:27537921
Guilliams, Kristin; Rosen, Max; Buttram, Sandra; Zempel, John; Pineda, Jose; Miller, Barbara; Shoykhet, Michael
Refractory status epilepticus (RSE) is a life-threatening emergency, demonstrating, by definition, significant pharmacoresistance. We describe five cases of pediatric RSE treated with mild hypothermia. Retrospective chart review was performed of records of children who received hypothermia for RSE at two tertiary-care pediatric hospitals between 2009 and 2012. Five children with RSE received mild hypothermia (32-35°C). Hypothermia reduced seizure burden during and after treatment in all cases. Prior to initiation of hypothermia, four children (80%) received pentobarbital infusions to treat RSE, but relapsed after pentobarbital discontinuation. No child relapsed after treatment with hypothermia. One child died after redirection of care. Remaining four children were discharged. This is the largest pediatric case series reporting treatment of RSE with mild hypothermia. Hypothermia decreased seizure burden during and after pediatric RSE and may prevent RSE relapse. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
Jeong, Hye Seon; Oh, Eung Seok; Lee, Ji Hee; Kim, Jae Moon
Status epilepticus (SE) in pregnancy is very rare, and there are only a few case reports of refractory SE (RSE) during pregnancy. The patient was a 27-year-old primigravida woman with a 21-year history of seizures from cortical dysplasia. At 23 weeks of pregnancy, the patient’s seizure frequency progressively increased, and the patient came to the ER in a confused mental state and with intermittent convulsive movements of her left arm. Electroencephalography (EEG) revealed repeated seizures. She was admitted to the ICU, and continuous EEG monitoring was done. Treatment was immediately started with various anti-SE medications, but her SE was not controlled. A cesarean section was done, and SE spontaneously stopped two weeks after the parturition. Parturition may be beneficial and the best treatment option in pregnant patients with RSE. PMID:24649442
Claassen, Jan; Riviello, James J; Silbergleit, Robert
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.
Illán-Gala, Ignacio; Díaz de Terán, Francisco Javier; Alonso, Pablo; Aguilar-Amat, María-José
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. Clinical improvement and resolution of EEG abnormalities were observed following the administration of intravenous levetiracetam and lacosamide. Other causes of NCSE were ruled out, and antiepileptic drugs were slowly tapered off without new episodes of abnormal behavior after three months of follow-up. We have reported the first case of NCSE secondary to paclitaxel–cremophor. Neurologists and oncologists should consider NCSE as an unusual complication of treatment with paclitaxel–cremophor in patients without a history of epilepsy. PMID:26106578
Kubota, Yuichi; Nakamoto, Hidetoshi; Kawamata, Takakazu
Continuous EEG monitoring (cEEG) has been recently applied in a neurocritical care setting in the US. The purpose of cEEG is primarily to detect nonconvulsive status epilepticus (NCSE) and secondarily, to evaluate the treatment of NCSE. It is difficult to diagnose NCSE in cEEG because of its variability. In the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology 2012, EEG localization is placed under major term 1 and is classified as Lateralized (L), Generalized (G), Bilateral Independent (BI), and Multifocal (Mf). Morphology is placed under major term 2 and is classified as periodic, rhythmic, and spike-and-wave. Although there are no unequivocal criteria for the diagnosis of NCSE, the appearance of spatial and temporal changes in the EEG is essential for diagnosis.
Guilliams, Kristin; Rosen, Max; Buttram, Sandra; Zempel, John; Pineda, Jose; Miller, Barbara; Shoykhet, Michael
SUMMARY Purpose Refractory status epilepticus (RSE) is a life-threatening emergency, demonstrating, by definition, significant pharmacoresistance. We describe five cases of pediatric RSE treated with mild hypothermia. Methods Retrospective chart review was performed of records of children who received hypothermia for RSE at two tertiary-care pediatric hospitals between 2009 and 2012. Key Findings Five children with RSE received mild hypothermia (32–35°C). Hypothermia reduced seizure burden during and after treatment in all cases. Prior to initiation of hypothermia, four children (80%) received pentobarbital infusions to treat RSE, but relapsed after pentobarbital discontinuation. No child relapsed after treatment with hypothermia. One child died after redirection of care. Remaining four children were discharged. Significance This is the largest pediatric case series reporting treatment of RSE with mild hypothermia. Hypothermia decreased seizure burden during and after pediatric RSE and may prevent RSE relapse. PMID:23906244
Zeiler, F A; Zeiler, K J; Kazina, C J; Teitelbaum, J; Gillman, L M; West, M
Our goal was to perform a systematic review of the literature on the use of intravenous lidocaine in adults for status epilepticus (SE) and refractory status epilepticus (RSE) to determine its impact on seizure control. All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to November 2014), and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. Overall, 13 studies were identified, with 11 manuscripts and 2 meeting abstracts. Seventy-six adult patients were treated for 82 episodes of SE/RSE. Patients had varying numbers of anti-epileptic drugs (AEDs), 1-12, on board prior to lidocaine therapy. During 69 of the 82 (84.1%) episodes of SE/RSE, phenytoin was on board. The dose regimen of lidocaine varied, with some utilizing bolus dosing alone; others utilizing a combination of bolus and infusion therapy. Overall, 70.7% of seizures responded to lidocaine, with complete cessation and greater than 50% reduction seen in 64.1% and 6.1% respectively. Patient outcomes were sparingly reported. There currently exists level 4, GRADE C evidence to support the consideration of lidocaine for SE and RSE in the adult population. Thus there is currently weak evidence to support the use of lidocaine in this context. Further prospective studies of lidocaine administration in this setting are warranted. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Easley, R B; Cooperstock, M S; Tobias, J D
Status epilepticus from cat-scratch encephalopathy is often recalcitrant to usual therapies, causing treatment to focus on critical care management of the patient that may require aggressive interventions, such as continuous pentobarbital administration. We describe two children whose initial clinical presentation of cat-scratch disease was status epilepticus with normal cerebrospinal fluid studies. A history of cat exposure (specifically, kitten and/or fleas), regional lymphadenopathy, and a papule or inoculation site should be sought, but are not essential for diagnosis. The presumptive diagnosis of cat-scratch disease can be made by serology alone even in the absence of classic diagnostic criteria. Our two cases and other reports in the literature show a favorable prognosis in most cases, despite the occurrence of status epilepticus. The diagnosis of cat-scratch disease should be strongly considered in all children with unexplained status epilepticus or encephalopathy and serologic testing for Bartonella henselae should be done.
de Assis, Telma M.R.; Costa, Gersonita; Bacellar, Aroldo; Orsini, Marco; Nascimento, Osvaldo J.M.
The aim of the study was to review the epidemiology, clinical profile and discuss the etiology, prognosis and treatment options in patients aged 60 years or older presenting with status epilepticus. We performed a systematic review involving studies published from 1996 to 2010, in Medline/PubMed, Scientific Electronic Library on line (Scielo), Latin-American and Caribbean Center of Health Sciences Information (Lilacs) databases and textbooks. Related articles published before 1996, when relevant for discussing epilepsy in older people, were also included. Several population studies had shown an increased incidence of status epilepticus after the age of 60 years. Status epilepticus is a medical and neurological emergency that is associated with high morbidity and mortality, and is a major concern in the elderly compared to the general population. Prompt diagnosis and effective treatment of convulsive status epilepticus are crucial to avoid brain injury and reduce the fatality rate in this age group. PMID:23355930
Sahin, M; Riviello, J J
Barbiturate anesthesia, which is commonly used for refractory status epilepticus, is an effective treatment, but with many significant complications. The relationship between the duration of this extreme therapy and the ultimate outcome of refractory status epilepticus has not been well studied. We report a 7-year-old girl who presented with refractory status epilepticus secondary to presumed encephalitis with a focal lesion on cranial magnetic resonance imaging. She was treated for 70 days with high-dose antiepileptic drugs and recovered with a residual seizure disorder. This case suggests that, if the status epilepticus is due to a reversible cause such as encephalitis, neurologic recovery may occur despite this very prolonged course of extreme therapy.
Broomall, Eileen; Natale, JoAnne E; Grimason, Michele; Goldstein, Joshua; Smith, Craig M; Chang, Celia; Kanes, Stephen; Rogawski, Michael A; Wainwright, Mark S
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. © 2014 American Neurological Association.
Holzer, Franz Josef; Seeck, Margitta; Korff, Christian M
The understanding of immunological mechanisms underlying some forms of epilepsy and encephalitis has rapidly increased for the last 10 years leading to the concept of status epilepticus of autoimmune origin. Actual treatment recommendations regarding autoimmune status epilepticus are based on retrospective case studies, pathophysiological considerations and experts' opinion. In addition, there are no clear indicators to predict outcome. In situations where autoimmune mechanisms are suspected in patients with status epilepticus, there is evidence that earlier treatment is related to better outcome. Increased awareness is mandatory to decrease the number of patients with major neurological problems or fatal outcome, which is overall about 50%. We here summarize findings of all pediatric and adult patients reported to date, and review the current state of knowledge in the field of immune therapeutic approaches of status epilepticus.
Al-Qahtani, Mashael; Khan, Sonia A; Kabiraj, Mohammed; Khoja, Waleed A
Ictal aphasia in adults is a rare phenomenon. Most reported cases manifest with non-fluent (Broca) aphasia. Ictal fluent (Wernicke) aphasia is less common. We report a 47-year-old, right-handed woman that presented with recurrent episodes of non-convulsive seizures in the form of Wernicke's aphasia for 2 weeks. An MRI of the brain showed an old cerebral infarction in the left parieto-occipital area. Scalp EEG revealed continuous periodic sharp waves at the left temporal regions with diffusion to the whole left hemisphere and at occasions to the right. This is followed by variable periods of post ictal slowing. Recurrence of the described ictal pattern was noted. Management of status epilepticus was started in the form of intravenous diazepam and a loading dose of phenytoin and phenobarbitone. After treatment, she improved clinically and the EEG improved with disappearance of the left temporal ictal rhythm and normalization of the EEG background. Thus, establishing the diagnosis of non-convulsive partial status epilepticus manifesting as ictal aphasia.
Mikulecká, A; Krsek, P; Hlinák, Z; Druga, R; Mares, P
An animal model of human complex partial status epilepticus induced by lithium chloride and pilocarpine administration was developed in our laboratory. The objective of the study was to provide a detailed analysis of both ictal and postictal behavior and to quantify seizure-related morphological damage. In order to determine the animal's responsiveness to either visual or olfactory stimuli, adult male rats were submitted to the following behavioral paradigms: the object response test, the social interaction test, and the elevated plus-maze test. The rotorod test was used to evaluate motor performance. Two weeks after status epilepticus, brains were morphologically examined and quantification of the brain damage was performed. Profound impairment of behavior as well as responsiveness to exteroceptive stimuli correlated with the occurrence of epileptic EEG activity. When the epileptic EEG activity ceased, responsiveness of the pilocarpine-treated animals was renewed. However, remarkable morphological damage persisted in the cortical regions two weeks later. This experimental study provides support for the clinical evidence that even nonconvulsive epileptic activity may cause brain damage. We suggest that the model can be used for the study of both functional and morphological consequences of prolonged nonconvulsive seizures.
Rogawski, Michael A.; Loya, Carlos M.; Reddy, Kiran; Zolkowska, Dorota; Lossin, Christoph
SUMMARY Benzodiazepines are the current first-line standard-of-care treatment for status epilepticus but fail to terminate seizures in about one-third of cases. Synaptic GABAA receptors, which mediate phasic inhibition in central circuits, are the molecular target of benzodiazepines. As status epilepticus progresses, these receptors are internalized and become functionally inactivated, conferring bezodiazepine resistance, which is believed to be a major cause of treatment failure. GABAA receptor positive allosteric modulator neuroactive steroids, such as allopregnanolone, also potentiate synaptic GABAA receptors, but in addition they enhance extrasynaptic GABAA receptors that mediate tonic inhibition. Extrasynaptic GABAA receptors are not internalized and desensitization of these receptors does not occur during continuous seizures in status epilepticus models. Here we review the broad-spectrum antiseizure activity of allopregnanolone in animal seizure models and the evidence for its activity in models of status epilepticus. We also demonstrate that allopregnanolone inhibits ongoing behavioral and electrographic seizures in a model of status epilepticus, even when there is benzodiazepine resistance. Parenteral allopregnanolone may provide an improved treatment for refractory status epilepticus. PMID:24001085
Holtkamp, Martin; Meierkord, Hartmut
Nonconvulsive status epilepticus (NCSE) comprises a group of syndromes that display a great diversity regarding response to anticonvulsants ranging from virtually self-limiting variants to entirely refractory forms. Therefore, treatment on intensive care units (ICUs) is required only for a selection of cases. The aetiology and clinical form of NCSE are strong predictors for the overall prognosis. Absence status epilepticus is commonly seen in patients with idiopathic generalized epilepsy and is rapidly terminated by low-dose of benzodiazepines. The management of complex partial status epilepticus is straightforward in patients with pre-existing epilepsy, but poses major problems if occurring in the context of acute brain lesions. Subtle status epilepticus represents the late stage of undertreated previous overt generalized convulsive status epilepticus and always requires aggressive ICU treatment. Within the intensive care setting, the diagnostic challenge may be seen in the difficulty in delineating nonepileptic conditions such as posthypoxic, metabolic or septic encephalopathies from NCSE. Although all important forms are considered, the focus of this review lies on clinical presentations and electroencephalogram features of comatose patients treated on ICUs and possible diagnostic pitfalls. PMID:21694817
Naito, Kosuke; Hashimoto, Takao; Ikeda, Shu-ichi
Described here is the case of a patient with liver cirrhosis who developed bilateral temporo-occipital lobe lesions on MRI and Klüver-Bucy syndrome following status epilepticus. Herpes encephalitis, paraneoplastic syndrome, Hashimoto's encephalopathy, reversible posterior leukoencephalopathy syndrome, mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode syndrome were judged not to be involved on the basis of laboratory results. The possible cause of the temporo-occipital lesions on MRI in this patient was cortical damage related mainly to status epilepticus and partially to coexisting hepatic encephalopathy.
Haberlandt, E; Sigl, S Baumgartner; Scholl-Buergi, S; Karall, D; Rauchenzauner, M; Rostásy, K
Levetiracetam (LEV) is approved as second line treatment for partial onset seizures in adults and children older than four years of age. Recently, an intravenous formulation was developed as an alternative to standard oral medication. We report the successful treatment of two children suffering from myoclonic status epilepticus with intravenous LEV. Intravenous application of LEV was safe and not associated with significant side effects. In conclusion, intravenous application of LEV appears to be a further option in treatment of children with myoclonic status epilepticus.
Scholtes, F B; Renier, W O; Meinardi, H
The incidence of non-convulsive status epilepticus (NCSE) in The Netherlands is not known. Files of admissions in the years 1980-7 were studied from 40 adult patients (older than 15 years) with complex partial status epilepticus (CPSE) and 25 with absence status epilepticus (ASE). The clinical presentation sometimes made distinction between CPSE and ASE possible. Focal clinical signs were more frequent in CPSE; a fluctuating level of consciousness was more often present in ASE. All patients, but one, with ASE and most patients with CPSE (28) were known to have had previous epilepsy. Outcome in ASE was good in all. Outcome in CPSE depended on the underlying cause and quality of treatment. In three patients inadequate treatment probably contributed to morbidity. PMID:8676169
Goyal, Manoj Kumar; Chakravarthi, Sudheer; Modi, Manish; Bhalla, Ashish; Lal, Vivek
The treatment protocols for status epilepticus (SE) range from small doses of intravenous benzodiazepines to induction of coma. The pros and cons of more aggressive treatment regimen remain debatable. The importance of an index need not be overemphasized which can predict outcome of SE and guide the intensity of treatment. We tried to evaluate utility of one such index Status epilepticus severity score (STESS). 44 consecutive patients of SE were enrolled in the study. STESS results were compared with various outcome measures: (a) mortality, (b) final neurological outcome at discharge as defined by functional independence measure (FIM) (good outcome: FIM score 5-7; bad outcome: FIM score 1-4), (c) control of SE within 1h of start of treatment and (d) need for coma induction. A higher STESS score correlated significantly with poor neurological outcome at discharge (p=0.0001), need for coma induction (p=0.0001) and lack of response to treatment within 1h (p=0.001). A STESS of <3 was found to have a negative predictive value of 96.9% for mortality, 96.7% for poor neurological outcome at discharge and 96.7% for need of coma induction, while a STESS of <2 had negative predictive value of 100% for mortality, coma induction and poor neurological outcome at discharge. STESS can reliably predict the outcome of status epilepticus. Further studies on STESS based treatment approach may help in designing better therapeutic regimens for SE. Copyright © 2015 Elsevier B.V. All rights reserved.
Ong, Cheung-Ter; Wong, Yi-Sin; Sung, Sheng-Feng; Wu, Chi-Shun; Hsu, Yung-Chu; Su, Yu-Hsiang; Hung, Ling-Chien
Status epilepticus (SE) is an important neurological emergency. Early diagnosis could improve outcomes. Traditionally, SE is defined as seizures lasting at least 30 min or repeated seizures over 30 min without recovery of consciousness. Some specialists argued that the duration of seizures qualifying as SE should be shorter and the operational definition of SE was suggested. It is unclear whether physicians follow the operational definition. The objective of this study was to investigate whether the incidence of SE was underestimated and to investigate the underestimate rate. This retrospective study evaluates the difference in diagnosis of SE between operational definition and traditional definition of status epilepticus. Between July 1, 2012, and June 30, 2014, patients discharged with ICD-9 codes for epilepsy (345.X) in Chia-Yi Christian Hospital were included in the study. A seizure lasting at least 30 min or repeated seizures over 30 min without recovery of consciousness were considered SE according to the traditional definition of SE (TDSE). A seizure lasting between 5 and 30 min was considered SE according to the operational definition of SE (ODSE); it was defined as underestimated status epilepticus (UESE). During a 2-year period, there were 256 episodes of seizures requiring hospital admission. Among the 256 episodes, 99 episodes lasted longer than 5 min, out of which 61 (61.6%) episodes persisted over 30 min (TDSE) and 38 (38.4%) episodes continued between 5 and 30 min (UESE). In the 38 episodes of seizure lasting 5 to 30 minutes, only one episode was previously discharged as SE (ICD-9-CM 345.3). Conclusion. We underestimated 37.4% of SE. Continuing education regarding the diagnosis and treatment of epilepsy is important for physicians.
Brigo, Francesco; Trinka, Eugen
Millions of people surf the Internet every day as a source of health-care information looking for materials about symptoms, diagnosis, treatments and their possible adverse effects, or diagnostic procedures. Google is the most popular search engine and is used by patients and physicians to search for online health-related information. This study aimed to evaluate changes in Google search behavior occurring in English-speaking countries over time for the term "status epilepticus" (SE). Using Google Trends, data on global search queries for the term SE between the 1st of January 2004 and 31st of December 2014 were analyzed. Search volume numbers over time (downloaded as CSV datasets) were analyzed by applying the "health" category filter. The research trends for the term SE remained fairly constant over time. The greatest search volume for the term SE was reported in the United States, followed by India, Australia, the United Kingdom, Canada, the Netherlands, Thailand, and Germany. Most terms associated with the search queries were related to SE definition, symptoms, subtypes, and treatment. The volume of searches for some queries (nonconvulsive, focal, and refractory SE; SE definition; SE guidelines; SE symptoms; SE management; SE treatment) was enormously increased over time (search popularity has exceeded a 5000% growth since 2004). Most people use search engines to look for the term SE to obtain information on its definition, subtypes, and management. The greatest search volume occurred not only in developed countries but also in developing countries where raising awareness about SE still remains a challenging task and where there is reduced public knowledge of epilepsy. Health information seeking (the extent to which people search for health information online) reflects the health-related information needs of Internet users for a specific disease. Google Trends shows that Internet users have a great demand for information concerning some aspects of SE
Gallentine, William B; Hunnicutt, Addie S; Husain, Aatif M
The objective of this study was to investigate the utility of levetiracetam (LEV) in children with refractory status epilepticus (RSE). Records of children with RSE who received LEV as adjunctive therapy were reviewed. Over a 7-year period, 11 children had received LEV for RSE. Age ranged from 2 days to 9 years (median = 2.5 months). Prior to administration of LEV, the number of anticonvulsants used to treat RSE ranged from 2 to 7 (median = 3). Starting doses of LEV ranged from 15 to 70 mg/kg (median = 30 mg/kg). LEV was felt to be of benefit in 45% (5/11) of cases, resulting in either resolution of RSE or successful weaning of patients off continuous infusions of other anticonvulsants. In 27% (3/11), response to LEV was unclear as other medications were either added or increased concomitantly with LEV use. The median latency to cessation of RSE following LEV initiation was 1.5 days (range = 1-8 days). All responding patients were on LEV doses >or= 30 mg/kg/day (median 40 mg/kg/day). No significant adverse effects of LEV were reported. LEV may be an effective and safe adjuvant therapy in children with RSE.
Toledo, Manuel; Munuera, Josep; Sueiras, Maria; Rovira, Rosa; Alvarez-Sabín, José; Rovira, Alex
Ictal-MRI studies including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and MR-angiography (MRA) in patients with aphasic status epilepticus (ASE) are lacking. In this report, we aim to describe the consequences of the ASE on DWIs and its impact on cerebral circulation. We retrospectively studied eight patients with ASE confirmed by ictal-EEG, who underwent ictal-MRI shortly after well-documented onset (mean time delay 3 h). ASE consisted in fluctuating aphasia, mostly associated with other subtle contralateral neurological signs such as hemiparesia, hemianopia, or slight clonic jerks. In MRI, six patients showed cortical temporoparietal hyperintensity in DWI and four of them had also ipsilateral pulvinar lesions. Five patients showed close spatial hyperperfusion areas matching the DWI lesions and an enhanced blow flow in the middle cerebral artery. Parenchymal lesions and hemodynamic abnormalities were not associated with seizure duration or severity in any case. The resolution of DWI lesions at follow-up MRI depended on the length of the MRIs interval. In patients with ASE, lesions on DWI in the temporo-parietal cortex and pulvinar nucleus combined with local hyperperfusion can be observed, even when they appear distant from the epileptic focus or the language areas.
KUBOTA, Yuichi; NAKAMOTO, Hidetoshi; KAWAMATA, Takakazu
Herein, we review the current state of nonconvulsive status epilepticus (NCSE). NCSE has recently been recognized as one of the causes of unexplained impaired consciousness in the neurosurgical or neurocritical setting. The causes of NCSE include not only central nervous system disorders such as craniotomy, stroke, traumatic brain injury, and central nervous system inflammation, but also severe critical conditions such as sepsis and uremia, among others. NCSE shows no overt clinical manifestations; therefore, prompt and correct diagnosis is difficult. The diagnosis of NCSE should be made by electroencephalogram (EEG), especially continuous EEG (CEEG) monitoring, because NCSE is caught only by prolonged recording. However, the interpretation of the EEG findings is also challenging because of the varying EEG characteristic of NCSE. While the diagnosis should be based on temporal or spatial EEG changes, several definitions and criteria have been proposed, and uniform, universal criteria are still lacking. Once NCSE is diagnosed, antiepileptic drugs (AEDs) should be aggressively administrated. Although there are no standardized international therapeutic guidelines, several AEDs have been attempted in clinical practice in other countries, including fosphenytoin, midazolam, levetiracetam, and valproate. Particularly, several AEDs should be considered prior to using anesthetics. Finally, the prognosis of NCSE depends on the cause thereof; however, in general, earlier intervention for NCSE appears important in terms of better recovery. PMID:27580931
Takahashi, Megumi; Okudera, Hiroshi
According to the 2010 neuroresuscitation guideline, status epilepticus (SE) is a critical condition that causes respiratory and circulation dysfunction, including "acute consciousness disturbance" and "elevated intracranial pressure." There are two types of SE: general convulsive SE (GCSE) and nonconvulsive SE (NCSE). GCSE is easily diagnosed because the patients show continuous convulsions. In contrast, NCSE can only be diagnosed by electroencephalography (EEG), which can delay diagnosis. Moreover, GCSE and NCSE occasionally manifest in the same patient and alternate. Here, we describe the case of a 64-year-old male patient who experienced losses of consciousness mimicking stroke. We could not diagnose these episodes as NCSE until the patient had a general continuous convulsion. In this case, the delayed diagnosis of NCSE resulted in uncontrollable GCSE that required intensive management, including mechanical ventilation under sedation. It is important to recognize that NCSE can cause consciousness disturbance and to initiate treatment as soon as possible to improve patient prognosis. This could be achieved by performing an EEG earlier, such as at the scene of emergencies.
Greiner, Hansel M; Holland, Katherine; Leach, James L; Horn, Paul S; Hershey, Andrew D; Rose, Douglas F
A high prevalence of nonconvulsive status epilepticus (NCSE) has been reported in critically ill adults and neonates. Recent prospective pediatric studies focus on critically ill children and show wide variability in the frequency of NCSE. This study examines prevalence of pediatric NCSE regardless of inpatient setting and retrospectively identifies risk factors indicating a need for urgent continuous EEG. Medical records from patients aged 3 months to 21 years were identified either by (1) searching a clinical EEG database (n = 18) or (2) consecutive inpatient EEG referrals for NCSE over an 8-month period (n = 57). Seventy-five children, mean age of 7.8 years, were studied. NCSE was identified in 26 patients (35%) and in 8 of 57 (14%) patients referred for possible NCSE. More than half of the patients referred were outside of the ICU. A witnessed clinical seizure was observed in 24 of 26 (92%) patients with NCSE. Acute cortical neuroimaging abnormalities were significantly more frequent in patients with NCSE. The presence of clinical seizures and acute neuroimaging abnormality was associated with an 82% probability of NCSE. All but 1 patient with NCSE had electrographic or electroclinical seizures within the first hour of monitoring. A high prevalence of NCSE was observed, comparable to adult studies, but within a wider range of inpatient settings. Children with acute encephalopathy should undergo continuous EEG. This evaluation is more urgent if certain clinical risk factors are present. Optimal duration of monitoring and the effect of NCSE on prognosis should be studied.
Gedik, Ahmet H; Demirkol, Demet; Tatlı, Burak; Bayraktar, Suleyman; Alkan, Alpay; Karabocuoglu, Metin; Yuksel, Adnan
Refractory status epilepticus is a prolongation of status epilepticus despite anticonvulsant therapy with two or three medications in proper doses; it is defined as malignant status epilepticus if it takes weeks or months. Intravenous immunoglobulin, high-dose steroids, magnesium infusion, pyridoxine, hypothermia, ketogenic diet, electroconvulsive therapy, and surgical therapy are the other treatment options for status epilepticus. Our 5-year-old male patient was hospitalized at our pediatric intensive care unit because of status epilepticus secondary to meningoencephalitis. No response could be obtained with many medical and nonmedical therapies in our patient, who developed malignant status epilepticus with unknown etiology. Therapeutic plasma exchange was applied as convulsions continued. Ours is the first child for whom therapeutic plasma exchange was successfully applied because of malignant refractory status epilepticus secondary to meningoencephalitis. Therapeutic plasma exchange may be a treatment option for children with refractory status epilepticus following presumed meningoencephalitis. Copyright © 2014 Elsevier Inc. All rights reserved.
Dave, Hina N; Eugene Ramsay, Richard; Khan, Fawad; Sabharwal, Vivek; Irland, Megan
An 8-year-old girl treated at our facility for superrefractory status epilepticus was found to have a low pyridoxine level at 5 μg/L. After starting pyridoxine supplementation, improvement in the EEG for a 24-hour period was seen. We decided to look at the pyridoxine levels in adult patients admitted with status epilepticus. We reviewed the records on patients admitted to the neurological ICU for status epilepticus (SE). Eighty-one adult patients were identified with documented pyridoxine levels. For comparison purposes, we looked at pyridoxine levels in outpatients with epilepsy (n=132). Reported normal pyridoxine range is >10 ng/mL. All but six patients admitted for SE had low normal or undetectable pyridoxine levels. A selective pyridoxine deficiency was seen in 94% of patients with status epilepticus (compared to 39.4% in the outpatients) which leads us to believe that there is a relationship between status epilepticus and pyridoxine levels. Copyright © 2015 Elsevier Inc. All rights reserved.
Muramoto, Emiko; Mizobuchi, Masahiro; Sumi, Yoshihiro; Sako, Kazuya; Nihira, Atsuko; Takeuchi, Akiko; Nakamura, Hirohiko
Intravenous phenobarbital (IV-PB) therapy was launched in Japan in October 2008. We retrospectively investigated its efficacy and tolerability in patients with status epilepticus. Forty-three consecutive patients received IV-PB for status epilepticus between June 2009 and April 2011. Among them, 39 patients had underlying diseases, which included acute diseases in 19 patients and chronic conditions in 20 patients. Although 18 patients had been taking antiepileptic drugs (AEDs) before the occurrence of status epilepticus, the blood AED concentrations in 8 patients was below the therapeutic levels. Before the administration of IV-PB, 39 patients were treated with intravenous benzodiazepine, 17 patients were treated with intravenous phenytoin, and 15 patients with intravenous infusion of lidocaine. The initial doses of IV-PB ranged from 125 to 1,250 mg (1.9-20.0 mg/kg). Additional doses of IV-PB were required in 12 patients. Seizures were controlled in 35 patients (81%) after IV-PB administration. Cessation of status epilepticus was attained in 24 patients after the initial dose and in 11 patients after additional doses. There were no serious adverse effects, although respiratory suppression was observed in 3 patients and drug eruption was observed in 1 patient. IV-PB is relatively safe and effective for controlling status epilepticus. If the first dose is not effective, additional doses are required up to the recommended maximum dose.
This paper reviews the clinical trials in acute repetitive seizures and in tonic-clonic status epilepticus. There are good randomised controlled studies on the use of benzodiazepines in early status epilepticus, but an inadequate trial base in the later stages. Therapy has therefore to be based on open studies, although in the later stages there is also a dearth of open data. Tonic-clonic status epilepticus is a medical emergency and a condition with a significant mortality. The lack of information compromises optimal therapy. This paper reviews the reasons for the lack of data and the problems associated with collecting data. It is proposed that, in the first instance, the best way of improving the quality of evidence would be a multinational case registry of existing practice.
Goodkin, Howard P.; Yeh, Jwu-Lai; Kapur, Jaideep
Status epilepticus is a neurological emergency that results in mortality and neurological morbidity. It has been postulated that the reduction of inhibitory transmission during status epilepticus results from a rapid modification of GABAA receptors. However, the mechanism(s) that contributes to this modification has not been elucidated. We report, using an in vitro model of status epilepticus combined with electrophysiological and cellular imaging techniques, that prolonged epileptiform bursting results in a reduction of GABA-mediated synaptic inhibition. Furthermore, we found that constitutive internalization of GABAA receptors is rapid and accelerated by the increased neuronal activity associated with seizures. Inhibition of neuronal activity reduced the rate of internalization. These findings suggest that the rate of GABAA receptor internalization is regulated by neuronal activity and its acceleration contributes to the reduction of inhibitory transmission observed during prolonged seizures. PMID:15944379
Fuquay, Jennifer Maucher; Muha, Noah; Pennington, Paul L; Ramsdell, John S
Domoic acid (DA), a naturally occurring environmental toxin, has been observed to induce status epilepticus in humans, sea lions and pelicans. In a recent Sprague Dawley rat model, domoic acid dosing induced a state of status epilepticus which, after a symptom-free latent period without further dosing, progressed to recurrent spontaneous seizures, a hallmark of epilepsy. Certain individuals in this study also developed unusual behavioral changes, in particular an atypical aggression towards conspecifics. In this report we characterized the progression of aggressive behaviors after DA-induced status epilepticus and explored the relationship between aggressive behavior and recurrent spontaneous seizures. Experimental studies in this laboratory rat model are particularly relevant to California sea lions (Zapholus californianus), which show a spectrum of both epileptic and unusual behaviors, including aggression towards conspecifics in rehabilitation facilities, weeks to months after suspected exposure to domoic acid in the wild. Published by Elsevier Inc.
Dubey, Deepanshu; Kalita, Jayantee; Misra, Usha K
Status epilepticus (SE) is an important neurological emergency. It is defined as seizures lasting for 5 minutes or more or recurrent seizures without recovery of consciousness to baseline between the attacks. Refractory SE (RSE) is defined as SE persisting despite sufficient dose of benzodiazepines and at least one antiepileptic drug (AED), irrespective of time. Super refractory SE (SRSE) is defined as SE that continues for 24 hours or more after the use of anesthetic therapy, including cases that recur on weaning of the anesthestic agent. RSE occurs in 23%-48% of the patients and SRSE in approximately 22% of the patients with SE. In general, RSE occurs in patients with new-onset seizures rather than in patients with chronic epilepsy. The etiology of RSE in developing countries is dominated by central nervous system (CNS) infections and head injury compared to stroke and drug withdrawal in the developed countries. The treatment of RSE and SRSE is not evidence based. Following benzodiazepines, the second line antiepileptic drugs include sodium valproate, phenytoin, levetiracetam, and anesthetic drugs such as midazolam, phenobarbital, and propofol. Most intravenous anesthetic drugs produce hypotension and respiratory suppression; therefore, patients with RSE are managed in intensive care units (ICUs). In RSE patients, electroencephalogram (EEG) burst suppression with interburst interval of 2-20 s or even flat EEG has been tried. Recently, concerns have been raised on the safety of burst suppression in RSE and SRSE. The paucity of ICUs in developing countries limits the use of these management protocols. There is a need to explore intravenous AEDs with safer cardiovascular and respiratory profile for the management of SE.
Mazarati, Andrey; Bragin, Anatol; Baldwin, Roger; Shin, Don; Wilson, Charles; Sankar, Raman; Naylor, David; Engel, Jerome; Wasterlain, Claude G
To describe the natural history of chronic epilepsy after experimental self-sustaining status epilepticus (SSSE) and to correlate patterns of SSSE with ictal, interictal, and plastic changes that characterize chronic epilepsy. SSSE was induced in adult Wistar rats by 30-min intermittent electrical stimulation of the perforant path. In some animals, SSSE was treated by short-term administration of antiepileptic drugs (AEDs). After SSSE, EEG and animal behavior were monitored for =1 year. Some animals were killed to study mossy fiber sprouting in the dentate gyrus. Despite the high reproducibility of the electrographic and behavioral manifestations of SSSE, patterns of chronic epilepsy varied considerably among animals in terms of seizure frequency, initial seizure pattern at the onset of chronic epilepsy, and frequency of interictal spikes. Statistically significant correlations were found between spike frequency during SSSE and interictal spike frequency, as well as between the frequency of spontaneous seizures and degree of mossy fiber sprouting. Early treatment of SSSE prevented the occurrence of spontaneous seizures and significantly decreased frequency of interictal spikes. Late treatment of SSSE did not prevent spontaneous seizures, but significantly decreased their frequency, and eventually may lead to remission of epilepsy. SSSE leads after a "silent" period to chronic epilepsy, which is maintained for > or =1 year in the rat. The silence is only behavioral, because EEG paroxysmal activity is seen in every animal. In this model of SSSE, the timing of treatment is a major determinant of outcome. Early treatment reduces the incidence of chronic epilepsy, whereas late treatment only reduces its severity. The possibility that this reduction of the severity of epilepsy may led to spontaneous remissions merits further study.
Uda, Kazuhiro; Kitazawa, Katsuhiko
Febrile status epilepticus can have neurological sequelae. The type of sequelae, however, depend on the etiology, including infection due to viral agents such as the influenza virus. Respiratory syncytial virus (RSV) infection in childhood may also contribute to this. The aim of this study was therefore to characterize febrile status epilepticus associated with RSV infection, and to determine whether this type of infection is a risk factor for neurological sequelae in febrile status epilepticus. We reviewed the medical records of children aged ≤3 years with febrile status epilepticus who were admitted to a tertiary hospital between January 2007 and December 2011. The differences between the RSV-positive and RSV-negative groups were evaluated according to the demographic and clinical data. A total of 99 patients with febrile status epilepticus who had been tested for RSV infection were identified. Three patients in the RSV-positive group (n = 19) and four in the RSV-negative group (n = 80) presented with bronchiolitis. The incidence of intubation and anti-seizure drug treatment in the RSV-positive group was significantly higher than in the -negative group. While all of the patients in the RSV-negative group recovered completely, six patients in the RSV-positive group developed encephalopathy and profound neurological sequelae. In five of the six patients, diffusion-weighted magnetic resonance imaging showed subcortical white matter lesions. RSV infection in the absence of bronchiolitis can initially present as febrile status epilepticus and subsequently develop into acute encephalopathy with profound neurological sequelae. © 2017 Japan Pediatric Society.
Wilkes, Ryan; Tasker, Robert C
The critically ill mechanically ventilated child with ongoing seizures that are refractory to any treatment presents a distinct challenge in pediatric neurocritical care. The evidence base from randomized controlled trials on which anti-epileptic drug (AED) strategy should be used is inadequate. This review of refractory and super-refractory status epilepticus summarizes recent pediatric case series regarding definitions, the second-tier AED therapies once initial anticonvulsants have failed, and the experience of high-dose midazolam, barbiturate anesthesia, and volatile anesthetics for uncontrolled status epilepticus. Copyright © 2013 Elsevier Inc. All rights reserved.
Sánchez Fernández, Iván; Jackson, Michele C; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Chapman, Kevin E; Gaillard, William D; Gaínza-Lein, Marina; Glauser, Tracy A; Goldstein, Joshua L; Goodkin, Howard P; Helseth, Ashley; Kapur, Kush; McDonough, Tiffani L; Mikati, Mohamad A; Peariso, Katrina; Riviello, James; Tasker, Robert C; Topjian, Alexis A; Wainwright, Mark S; Wilfong, Angus; Williams, Korwyn; Loddenkemper, Tobias
To compare refractory convulsive status epilepticus (rSE) management and outcome in children with and without a prior diagnosis of epilepsy and with and without a history of status epilepticus (SE). This was a prospective observational descriptive study performed from June 2011 to May 2016 on pediatric patients (1 month-21 years of age) with rSE. We enrolled 189 participants (53% male) with a median (25th-75th percentile) age of 4.2 (1.3-9.6) years. Eighty-nine (47%) patients had a prior diagnosis of epilepsy. Thirty-four (18%) patients had a history of SE. The time to the first benzodiazepine was similar in participants with and without a diagnosis of epilepsy (15 [5-60] vs 16.5 [5-42.75] minutes, p = 0.858). Patients with a diagnosis of epilepsy received their first non-benzodiazepine (BZD) antiepileptic drug (AED) later (93 [46-190] vs 50.5 [28-116] minutes, p = 0.002) and were less likely to receive at least one continuous infusion (35/89 [39.3%] vs 57/100 [57%], p = 0.03). Compared to patients with no history of SE, patients with a history of SE received their first BZD earlier (8 [3.5-22.3] vs 20 [5-60] minutes, p = 0.0073), although they had a similar time to first non-BZD AED (76.5 [45.3-124] vs 65 [32.5-156] minutes, p = 0.749). Differences were mostly driven by the patients with an out-of-hospital rSE onset. Our study establishes that children with rSE do not receive more timely treatment if they have a prior diagnosis of epilepsy; however, a history of SE is associated with more timely administration of abortive medication. © 2016 American Academy of Neurology.
Langheinrich, Tobias Christoph; Chattopadhyay, Arup; Kuc, Sue; Reuber, Markus
We describe a patient who entered a stuporous state after receiving benzodiazepine treatment for generalized tonic-clonic status epilepticus. A diagnosis of generalized NCSE with tonic seizures was made on the basis of the clinical picture and response to barbiturate anaesthetic, although the EEG pattern was not typical of the changes previously described in tonic seizures-tonic status epilepticus. This report discusses the differential diagnosis of postictal stupor, nonconvulsive status epilepticus with tonic seizures and sedation caused by the emergency treatment of status epilepticus, and summarizes the literature on tonic seizures and tonic status epilepticus.
Vaccarezza, María; Silva, Walter; Maxit, Clarisa; Agosta, Guillermo
Super-refractory status epilepticus is that which persists despite suitable treatment with multiple anti-convulsive schemes, including prolonged coma with general anaesthetic. Different pharmacological treatment schemes have been proposed in these patients, including the use of a ketogenic diet. This study is a retrospective analysis of five patient records of children between 1 and 14 years of age, three of whom were diagnosed with FIRES (febrile infection-related epilepsy syndrome) and two with a diagnosis of refractory symptomatic partial epilepsy. The mean age was six years and the mean duration of the status epilepticus was 32 days. All the patients were given multiple therapeutic schemes; in all was obtained pharmacological coma with barbiturates to reach paroxysm-suppression pattern on electroencephalogram. Since the results of these strategies were not successful, a classical ketogenic diet was indicated. After starting the ketogenic diet, the clinical and electroencephalographic status epilepticus ceased in four patients with good tolerance. One patient did not respond and died. In patients with super-refractory status epilepticus, when different anticonvulsive schemes are unsuccessful, the ketogenic diet would be a good option. The ketogenic diet in this severe clinical situation is highly effective and safe.
Sinha, S; Prashantha, D K; Thennarasu, K; Umamaheshwara Rao, G S; Satishchandra, P
To analyse the underlying causes, therapeutic response and outcomes of convulsive refractory status epilepticus (RSE). This retrospective analysis was carried on 98 patients with RSE (age: 16.9+/-14.5 years). All had received a combination of parenteral benzodiazepine and phenytoin or phenobarbitone followed by other anti-epileptic drugs (AEDs). The clinical, EEG, imaging features of convulsive RSE and long-term seizure outcome were analysed. Seventy six patients had de novo RSE for the first time in life. The mean duration of RSE, before and during NICU admission was 3.4+/-3.2 days and 2.9+/-2.4 days respectively. The mean duration of NICU stay and mechanical ventilation was 17.4+/-14.5 was 14.4+/-12.8 days respectively. The precipitating factors included viral fever - 13, AEDs stoppage - 7 and alcohol - 1. EEG was abnormal in 81.5% of patients. CT and MRI were abnormal in 63.4% and 82.3% respectively. Thirty-four patients died and compared to those surviving, patients were older, had lesser duration of NICU stay and elevated CSF protein. Dependence for activities of daily living (ADL) at discharge was: recovered - 29, mild to moderate - 13 and severe - 22. Seizure outcome in 64 patients after 43.5+/-58.2 weeks were - seizure-free: 65.6%, one seizure: 21.8%, >1 seizure/month: 14.1%, and seizure recurrence requiring admission: 1.5%. After six and twelve months of follow up, the long-term seizure outcome were: seizure-free: 48.3% and 28.6%; one seizure: 27.6% and 38.1%; >1 seizure/month: 20.7% and 28.6%; and seizure recurrence requiring admission: 3.4% and 4.7% respectively. Among those survived 49 de novo RSE, about one-third developed post-SE symptomatic seizures after 30.1+/-54.4 weeks. Seizures could still be controlled in two-thirds of patients with convulsive RSE. About 30% of patients achieved long-term seizure freedom.
Fung, E Lw; Fung, B Bh
Convulsive status epilepticus is the most extreme form of seizure. It is a medical and neurological emergency that requires prompt and appropriate treatment. Treatment of convulsive status epilepticus is usually divided into stages/steps. The International League Against Epilepsy has released a new definition of status epilepticus that may help to unify the definition in future studies. Over the last few years new information has become available regarding its management. The Rapid Anticonvulsant Medication Prior to Arrival Trial demonstrated non-inferiority of intramuscular midazolam in early status epilepticus compared with intravenous lorazepam. Valproate and levetiracetam have also emerged as possible alternatives to phenytoin in established status epilepticus. The potential role of lacosamide in this stage of status epilepticus remains to be defined. The ongoing Established Status Epilepticus Treatment Trial may help to determine the most effective treatment for benzodiazepine-resistant status epilepticus. Management of refractory status epilepticus and super-refractory status epilepticus remains mostly non-evidence-based. Increasing recognition of a possible autoimmune aetiology has led to the use of immune-modulation in super-refractory status epilepticus. Ketamine is also increasingly used in this challenging condition. There are also reports of potential use of a ketogenic diet and magnesium.
Abend, Nicholas S
Electrographic seizures and electrographic status epilepticus are common in children with critical illness with acute encephalopathy, leading to increasing use of continuous EEG monitoring. Many children with electrographic status epilepticus have no associated clinical signs, so EEG monitoring is required for seizure identification. Further, there is increasing evidence that high seizure burdens, often classified as electrographic status epilepticus, are associated with worse outcomes. This review discusses the incidence of electrographic status epilepticus, risk factors for electrographic status epilepticus, and associations between electrographic status epilepticus and outcomes, and it summarizes recent guidelines and consensus statements addressing EEG monitoring in children with critical illness. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.
Walker, Matthew C; Williams, Robin S B
Starting with the established antiepileptic drug, valproic acid, we have taken a novel approach to develop new antiseizure drugs that may be effective in status epilepticus. We first identified that valproic acid has a potent effect on a biochemical pathway, the phosphoinositide pathway, in Dictyostelium discoideum, and we demonstrated that this may relate to its mechanism of action against seizures in mammalian systems. Through screening in this pathway, we have identified a large array of fatty acids and fatty acid derivatives with antiseizure potential. These were then evaluated in an in vitro mammalian system. One compound that we identified through this process is a major constituent of the ketogenic diet, strongly arguing that it may be the fatty acids that are mediating the antiseizure effect of this diet. We further tested two of the more potent compounds in an in vivo model of status epilepticus and demonstrated that they were more effective than valproic acid in treating the status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.
Belluzzo, Marco; Furlanis, Giovanni; Stragapede, Lara
Although status epilepticus is a common neurological emergency, literature about its short term functional disability is scarce and often difficult to interpret. The aim of the present study was to identify possible predictive factors of functional disability in a well-selected cohort of EEG-confirmed status epilepticus patients. We carried out a retrospective evaluation of clinical and radiologic parameters potentially affecting status epilepticus-related disability in a cohort of adult patients admitted to our institution between 2003 and 2013. Functional decline was defined as a ≥ 1 increase in the modified Rankin scale from preadmission to discharge. Seventy-nine patients fulfilled inclusion criteria (46% male). Median age was 69 years. History of epilepsy was present in 49% of patients. Deterioration occurred in 46 subjects (58%). Multivariate analysis revealed the following negative predicting factors for disability: normal neuroimaging (OR = 0.031) and presence of status epilepticus on hospital admission (OR = 0.127). Patients without evident brain lesions are at low risk of functional deterioration development. SE on admission portends a good prognosis as well, probably because it is more promptly treated and it develops in subjects with less systemic complications compared to those in hospital. Copyright © 2014 Elsevier B.V. All rights reserved.
Tiamkao, Somsak; Mayurasakorn, Nattakarn; Suko, Panit; Jitpimolmard, Suthipun; Arunpongpaisal, Suwanna; Phuttharak, Warinthorn; Auevitchayapat, Narong; Vannaprasaht, Suda; Tiamkao, Siriporn; Phunikhom, Kutcharin; Chaiyakum, Aporanee; Saengsuwan, Jiamjit
Refractory status epilepticus (RSE), defined as status epilepticus that fails to respond to first, second and third-line therapy. The RSE is associated with high morbidity and mortality. Treatment guidelines of RSE give a spectrum of options, such as, continuous intravenous (i.v.) midazolam (MDL), or continuous i.v. propofol (PRO) as alternatives to phenobarbital (PB) or continuous i.v. pentobarbital (PTB). To study the efficacy of very-high-dose phenobarbital (VHDPB) for treatment RSE. Retrospective study The authors collected and analyzed data from adult patients who were diagnosed with RSE. The authors present 10 patients with RSE who were treated with VHDPB. All of them were generalized convulsive status epilepticus (GCSE). Ages ranged from 16-86 years old (mean.: 43 years). PB dosage ranged 40-140 mg/kg/day (mean: 70 mg/kg/day). The duration of status epilepticus (SE) varied widely, ranged 1-44 days (mean: 7 days). PB level ranged 35.29-218.34 ug/mL (mean 88.1 ug/mL). RSE was controlled by VHDPB 70%, 30% were not controlled. VHDPB were considered as alternative treatment for RSE.
Doe De Maindreville, A; Gombert, C; Thiriaux, A; Chaunu, M; Bakchine, S
Hashimoto's Encephalopathy (HE) is a rare condition defined by the association of encephalopathy and autoimmune thyroiditis with increased levels of antithyroid antibodies. Presenting symptoms of HE may be quite variable. Although seizures are rather frequent, status epilepticus seems very rare (10 reported cases to date) and exceptionally revealing. We report the case of a 48-year-old female, who presented with a series of status epilepticus. The only positive result of the initial exploration was an increased level of antithyroid antibodies. The patient's condition improved only after initiation of corticosteroid treatment, which provided a stable remission. HE pathophysiology still remains poorly understood and controversial. Pathological data are sparse and provide variable pictures. Although an autoimmune mechanism looks very likely, the precise role of antithyroid antibodies is still discussed. A direct toxicity has not been demonstrated and antibodies could simply be a marker of impaired immunity. Occurrence of status epilepticus in HE could be related to the presence of active inflammation of cortical or para-cortical tissue, although such a hypothesis remains to be demonstrated. The diagnosis of HE should be systematically considered in patients with unexplained episodes of status epilepticus. Search for abnormal thyroid function and increased levels of antithyroid antibodies allow both early diagnosis and treatment, with a clear benefit for the patients.
Momcilović-Kostadinović, Dragana; Simonović, Perisa; Kolar, Dusan; Jović, Nebojsa
It is largely known that some antipsychotic agents could have proconvulsive and proepileptogenic effects in some patients and could induce EEG abnormalities as well. However, the association of status epilepticus with certain antipsychotic drugs has been very rarely reported. A case of an 18-year-old adolescent girl, with chlorpromazine therapy started for anxiety-phobic disorder was reported. Her personal history disclosed delayed psychomotor development. Shortly after the introduction of the neuroleptic chlorpromazine therapy in minimal daily dose (37.5 mg), she developed myoclonic status epilepticus, confirmed by the EEG records. Frequent, symmetrical bilateral myoclonic jerks and altered behavior were associated with bilateral epileptiform discharges of polyspikes and spike-wave complexes. This epileptic event lasted 3.5 hours and it was stopped by the parenteral administration ofvalproate and lorazepam; she was EEG monitored until stable remission. Status epilepticus as initial epileptic event induced by neuroleptic agent was not previously reported in our national literature. Introduction of chlorpromazine to a patient without history of seizures is associated with the evolution of an epileptic activity, including the occurrence of status epilepticus. Clinical evaluation of the risk factors possibly related to chlorpromazine-induced seizure is recommended in individual patients before administering this drug.
Sasidaran, K; Singhi, Sunit; Singhi, Pratibha
Acute seizure and status epilepticus constitute one of the major medical emergencies in children. Among children, the incidence ranges from 4-38/100,000 children per year respectively. The incidence in developing countries is somewhat higher because of infections. Although, the definition of status epilepticus is based on duration of seizures, the operational definition is to treat any child who is brought seizing to the emergency room, as status epilepticus. An urgent time bound approach is of paramount importance when managing a child in status epilepticus. Benzodiazepines remain the first line antiepileptic drugs in the emergency room; a long acting drug (Lorazepam) is preferred when available. This is followed by Phenytoin (20 mg/kg) loading. In patients refractory to above drugs, valproate (30 mg/kg) loading is commonly used and if effective, followed by an infusion (5 mg/kg/h) for seizure free period of 6 h. In non-responders, a trial of Levetiracetam (40 mg/kg infused at 5 mg/kg/min) can be used before starting benzodiazepine or thiopental coma (3-4 mg/kg loading dose, followed by 2 mg/kg/min infusion). When pharmacological coma is initiated, the child needs to be shifted to pediatric intensive care unit for proper monitoring and titration of medications.
Status epilepticus (SE) is a frequent neurologic emergency, one third of patients do not respond to treatment with benzodiazepines followed by a second antiepileptic drug. While initial treatment of complex partial SE is accordant to that of generalized convulsive SE, further management of refractory SE depends on the risk for acute complications and long-term clinical consequences. These risks are low in complex partial SE; therefore, in this clinical form anesthetics commonly are not used. Generalized convulsive SE-even in its early course-is a potentially life-threatening condition; therefore, prompt use of anesthetics is urgently required. Drugs of choice are barbiturates, midazolam, and propofol, all of which exhibit specific advantages and disadvantages. Up to now, data from clinical studies do not allow to prefer or to discard one of these anesthetics, therefore also barbiturates still should be used in refractory SE. A widely accepted in-house protocol for the management of initial and refractory SE is highly recommended.
Miller, Joseph B.; Nicholas, Katherine S.; Varelas, Panayiotis N.; Harsh, Donna M.; Durkalski, Valerie; Silbergleit, Robert; Wang, Henry E.
Introduction Limited data describe the frequency, timing, or indications for endotracheal intubation (ETI) in patients with status epilepticus. A better understanding of the characteristics of patients with status epilepticus requiring airway interventions could inform clinical care. We sought to characterize ETI use in patients with prehospital status epilepticus. Methods This study was a secondary analysis of the Rapid Anticonvulsant Medication Prior to Arrival Trial, a multi-center, randomized trial comparing intravenous lorazepam to intramuscular midazolam for prehospital status epilepticus treatment. Subjects received ETI in the prehospital, Emergency Department (ED), or inpatient setting at the discretion of caregivers. Results Of 1023 enrollments, 218 (21 %) received ETI. 204 (93.6 %) of the ETIs were performed in the hospital and 14 (6.4 %) in the prehospital setting. Intubated patients were older (52 vs 41 years, p < 0.001), and men underwent ETI more than women (26 vs 21 %, p = 0.047). Patients with ongoing seizures on ED arrival had a higher rate of ETI (32 vs 16 %, p < 0.001), as did those who received rescue anti-seizure medication (29 vs 20 %, p = 0.004). Mortality was higher for intubated patients (7 vs 0.4 %, p < 0.001). Most ETI (n = 133, 62 %) occurred early (prior to or within 30 min after ED arrival), and late ETI was associated with higher mortality (14 vs 3 %, p = 0.002) than early ETI. Conclusions ETI is common in patients with status epilepticus, particularly among the elderly or those with refractory seizures. Any ETI and late ETI are both associated with higher mortality. PMID:25623785
Poddar, Karan; Sharma, Rohan; Ng, Yu-Tze
Lacosamide is an antiepilepsy drug approved by the Food and Drug Administration for patients aged 17 years and older for partial-onset seizures as monotherapy or adjunctive therapy. We reviewed the use of intravenous lacosamide in children aged less than 17 years with status epilepticus. Children who received at least one dose of intravenous lacosamide for status epilepticus at our tertiary care children's hospital from December 2011 to March 2014 were studied. Status epilepticus was defined as continuous seizure activity for longer than 20 minutes or two or more recurrent seizures without regaining baseline level of awareness. Efficacy was defined as seizure freedom or more than 50% reduction of seizures within 24 hours of administering lacosamide. Nine children with a mean age of 5.7 years (range: three months to 16 years) were included. The mean initial or loading dose was 8.7 mg/kg, with seven of nine patients receiving a dose of 10 mg/kg. The average total amount of intravenous lacosamide administered within the initial 24 hours was 13.8 mg/kg. Lacosamide was found to be efficacious in seven of nine (77.8%) patients. Four patients (44.4%) became seizure free. Two patients continued to have status epilepticus within 24 hours of lacosamide administration. Bradycardia was observed in one patient. In children with status epilepticus, intravenous lacosamide was efficacious in 78% of the patients and 44% become seizure free. In addition, no significant adverse reactions were observed. An appropriate safe, effective initial, or loading dose may be 10 mg/kg. Copyright © 2016 Elsevier Inc. All rights reserved.
Cash, Sydney S.
Summary The traditional view of seizure activity is one in which there is extreme hypersynchronization. Although what is meant by hypersynchronization is rarely explicitly and fully defined it can be understood to imply large numbers of neurons firing together essentially simultaneously. In this discussion we will explore the possibility that seizures – both self-terminating and sustained in status - are not purely synchronous in time or in space. We will investigate the alternative possibility that much seizure activity represents spatiotemporal desynchronization. Furthermore, we will discuss the possibility that, in contrast to canonical views of epileptic activity, a high degree of synchronization is a pre-requisite for termination of the seizure rather than a marker of early and ongoing seizure activity. These ideas will be discussed with reference to results from our collaborative group based on microelectrode recordings in patients with epilepsy as well as to the many studies done by others in both patients and animal models. Finally, we will explore implications for these hypotheses in the treatment of patients with epilepsy and in status epilepticus. PMID:24001069
Adams, Scott J; Wong, Melody; Haji, Tahereh; Sohail, Shahmir; Almubarak, Salah
Absence status epilepticus is characterized by a prolonged state of impaired consciousness or altered sensorium with generalized electroencephalographic abnormalities. It is most commonly diagnosed in patients with known idiopathic generalized epilepsy; however, it may also be the first presentation of epilepsy. Due to the subtle and variable manifestations of the condition, absence status epilepticus may be underrecognized, particularly in children. We present the case of an 8-year-old boy who experienced two episodes of prolonged altered mental status, subsequently determined to be absence status epilepticus with idiopathic generalized epilepsy with phantom absences. We discuss the classification, pathophysiology, clinical presentation, and electroencephalographic findings of pediatric absence status epilepticus and provide a practical overview for management.
Sohail, Shahmir; Almubarak, Salah
Absence status epilepticus is characterized by a prolonged state of impaired consciousness or altered sensorium with generalized electroencephalographic abnormalities. It is most commonly diagnosed in patients with known idiopathic generalized epilepsy; however, it may also be the first presentation of epilepsy. Due to the subtle and variable manifestations of the condition, absence status epilepticus may be underrecognized, particularly in children. We present the case of an 8-year-old boy who experienced two episodes of prolonged altered mental status, subsequently determined to be absence status epilepticus with idiopathic generalized epilepsy with phantom absences. We discuss the classification, pathophysiology, clinical presentation, and electroencephalographic findings of pediatric absence status epilepticus and provide a practical overview for management. PMID:28042487
Madžar, Dominik; Kuramatsu, Joji B; Gerner, Stefan T; Huttner, Hagen B
The aim of this study was to assess factors associated with the use of topiramate (TPM) in refractory status epilepticus (RSE). We retrospectively reviewed RSE episodes over a 12-year period. Episodes treated with and without TPM were compared in terms of demographics, RSE characteristics, clinical course, and outcome in univariate and multivariate analyses. Subgroups defined by type of RSE were studied separately. Functional outcome was assessed with the modified Rankin Scale. Among 71 episodes, 17 (23.9%) were treated with TPM and seizure control was achieved in all of these. The results of unadjusted comparisons suggested a use of TPM in younger and healthier patients who received more perseverant treatment indicated by a higher number of antiepileptic drugs applied. In multivariate analysis adjusting for RSE duration, however, these associations lost significance. Furthermore, TPM was not a predictor of successful RSE termination in neither the overall cohort, nor in the subgroup of complex-partial RSE. After multivariate adjustment, no significant differences were observed between episodes treated with and without TPM in baseline characteristics, treatment, and outcome. Regarding the latter, this study does therefore not yield evidence for a particular efficacy of TPM in RSE. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Horino, Asako; Kawawaki, Hisashi; Fukuoka, Masataka; Tsuji, Hitomi; Hattori, Yuka; Inoue, Takeshi; Nukui, Megumi; Kuki, Ichiro; Okazaki, Shin; Tomiwa, Kiyotaka; Hirose, Shinichi
Clinical phenotypic expression of SSADH deficiency is highly heterogeneous, and some infants may develop refractory secondary generalized seizures. A 9-month-old boy manifested partial seizures, developing severe status epilepticus, and conventional antiepileptic drugs were ineffective. Use of ketamine contributed to the control of status epilepticus, achieving a reduction in frequency of partial seizures, and improving EEG findings without apparent complications. Diffusion-weighted images showed hyperintensities in the bilateral basal ganglia and fornix, and multiple T2 hyperintensity lesions were detected. (123)I-iomazenil (IMZ) SPECT revealed a decrease in binding of (123)I-iomazenil predominantly in the left temporal region by the 18th day of hospitalization. However, repeated IMZ-SPECT on the 46th day of hospitalization demonstrated almost no accumulation across a broad region, sparing the left temporal region. The patient showed rapid regression, refractory myoclonus, and severe progressive brain atrophy. IMZ-SPECT findings demonstrated reduced benzodiazepine receptor binding and its dynamic changes in an SSADH-deficient patient. Considering the down regulation of the GABAA receptor, ketamine should be included in pharmacotherapeutic strategies for treatment of refractory status epilepticus in SSADH-deficient patients. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Bello-Espinosa, Luis E
Analysis of infraslow EEG activity (ISA) has shown potential in the evaluation of patients with epilepsy and in the differentiation between focal and generalized epilepsies. Infraslow EEG activity analysis may also provide insights into the pathophysiology of refractory clinical and subclinical status epilepticus. The purpose of this report is to describe a girl with Sturge-Weber syndrome (SWS) who presented with a 96-h refractory encephalopathy and nonischemic hemiparesis and who was identified to have infraslow status epilepticus (ISSE), which successfully resolved after midazolam administration. The continuous EEG recording of a 5-year-old girl with known structural epilepsy due to Sturge-Weber syndrome is presented. The patient presented to the ED with acute confusion, eye deviation, and right hemiparesis similar to two previous admissions. Despite administration of lorazepam, fosphenytoin, phenobarbital, and valproic loads, the patient showed no improvement in the clinical condition after 48 h. The continuous video-EEG monitoring (VEM) showed continuous severe diffuse nonrhythmic asymmetric slowing but no apparent ictal activity on continuous conventional EEG recording settings. As brain CT, CTA, CTV, and complete MRI scans including DWI obtained within 72 h of presentation failed to demonstrate any ischemic changes, analysis of the EEG infraslow (ISA) activity was undertaken using LFF: 0.01 Hz and HFF: of 0.1 Hz, respectively. Continuous subclinical unilateral rhythmic ictal ISA was identified. This was only evident on the left hemisphere which correlated with the structural changes due to SWS. A trial of continuous 120 to 240 μg/kg/h of IV midazolam resulted in immediate resolution of the contralateral hemiparesis and encephalopathy. Continuous prolonged rhythmic ictal infraslow activity (ISA) can cause super-refractory subclinical focal status epilepticus. This has not been previously reported, and we propose that this be called infraslow status
Vyas, Devashish Dhiren; Dash, Gopal Krishna
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
Puoti, Gianfranco; Elefante, Andrea; Saracino, Dario; Capasso, Antonella; Cotrufo, Roberto; Anello, Clara Belluomo
New-onset refractory status epilepticus (NORSE) is a recently defined clinical entity that describes patients who present with status epilepticus of unclear etiology that is highly refractory to therapy. Magnetic resonance imaging (MRI) of NORSE usually discloses no specific abnormalities except for an occasional mild T2/FLAIR hyperintense signal of the mesial temporal lobe. Here, we report a peculiar case of NORSE in which brain MRI showed massive alteration of both temporal lobes, with features strongly supporting the diagnosis of herpes virus encephalitis, but lacking any laboratory evidence of viral infection in the blood and cerebrospinal fluid. It showed also striking signal alterations in the thalamus, which got worse in the course of the disease. This report emphasizes the possibility that seizure activity alone plays a critical role in both determining the disease and whether it will be self-sustaining.
Tassinari, Carlo A; Cantalupo, Gaetano; Rios-Pohl, Loreto; Giustina, Elvio Della; Rubboli, Guido
ESES (encephalopathy with status epilepticus during sleep) is an epileptic encephalopathy with heterogeneous clinical manifestations (cognitive, motor, and behavioral disturbances in different associations, and various seizure types) related to a peculiar electroencephalography (EEG) pattern characterized by paroxysmal activity significantly activated during slow sleep-that is, a condition of continuous spikes and waves, or status epilepticus, during sleep. The pathophysiologic mechanisms underlying this condition are still incompletely understood; recent data suggest that the abnormal epileptic EEG activity occurring during sleep might cause the typical clinical symptoms by interfering with sleep-related physiologic functions, and possibly neuroplasticity processes mediating higher cortical functions such as learning and memory consolidation. As in the myth of Penelope, the wife of Odysseus, what is weaved during the day will be unraveled during the night.
Webster, Danielle L; Gardner, Aaron H; Dye, Thomas J; Chima, Ranjit S
Human metapneumovirus (hMPV) is a relatively recent addition to the multiplicity of viruses causing respiratory illness in infants and children. Although well described in its ability to cause respiratory illness, there is limited data detailing the association of hMPV with neurologic complications. In this report, we describe 2 toddlers with hMPV infection who presented in status epilepticus and went on to develop respiratory failure. Both patients fully recovered over 2 weeks and were discharged from the hospital with no sequelae. The association between hMPV infection and neurologic complications is increasingly being reported in the literature. Clinicians should be aware of these uncommon manifestations of a common respiratory pathogen and consider testing for hMPV when managing pediatric patients who present with unexplained status epilepticus or encephalitis.
Jafarpour, Saba; Loddenkemper, Tobias
Recognition of nonconvulsive status epilepticus (NCSE) is gaining increasing attention in the assessment and evaluation of critically ill pediatric patients. The underlying cause of NCSE is often the most important factor in determining outcome. However, there is a growing body of literature suggesting that electrical seizure burden in NCSE also contributes to unfavorable outcomes. Determination of impact of NCSE on outcome based on current evidence involves consideration of heterogeneous study settings, study populations, and process of care and outcome measures. In addition, the lack of data on neurocognitive function prior to episodes of NCSE as well as limited long-term neurocognitive assessment data confines precise conclusions about neurocognitive changes. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.
Alford, Elizabeth L.; Wheless, James W.
Generalized convulsive status epilepticus (GCSE) is one of the most common neurologic emergencies and can be associated with significant morbidity and mortality if not treated promptly and aggressively. Management of GCSE is staged and generally involves the use of life support measures, identification and management of underlying causes, and rapid initiation of anticonvulsants. The purpose of this article is to review and evaluate published reports regarding the treatment of impending, established, refractory, and super-refractory GCSE in pediatric patients. PMID:26380568
Tian, L; Li, Y; Xue, X; Wu, M; Liu, F; Hao, X; Zhou, D
This study aims to determine the general frequency, mortality, and risk factors of super-refractory status epilepticus (SRSE) versus non-refractory status epilepticus (NRSE) and refractory status epilepticus (RSE). This work is a retrospective study. Clinical data of patients who were diagnosed with status epilepticus (SE) in the neurological ward and neuro-intensive care unit of West China Hospital from January 2009 to December 2012 were collected and analyzed. A total of 98 patients were included in the study. The percentages of NRSE, RSE, and SRSE were 67.3%, 20.4%, and 12.2%, respectively. Convulsive SE was the main seizure type among the three groups. The most common cause of NRSE was related to epilepsy (EP). However, 67.7% of SRSE cases were caused by acute encephalitis. Moreover, 47% of SE and 40% of RSE cases had a history of EP, whereas only 8.3% of SRSE cases had such history (P < 0.01). The percentage of patients with STESS ≤2 was lowest in the SRSE group without statistical significance (P > 0.05). The general mortality of SE was 7.1%, whereas that of SRSE was 50%. During follow-up, most SRSE patients who survived have developed symptomatic EP. This study was the first to use the statistical percentage of SRSE. Approximately 12.2% of SE cases will result in SRSE, which is a challenging medical situation for doctors. Patients with first episodes and acute encephalitis were also prone to develop SRSE. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Shetty, Ashok K.
Resveratrol (RESV; 3,5,4′-tri-hydroxy stilbene), a naturally occurring phytoalexin, is found at a high concentration in the skin of red grapes and red wine. RESV mediates a wide-range of biological activities, which comprise an increased life span, anti-ischemic, anti-cancer, antiviral, anti-aging and anti-inflammatory properties. Studies in several animal prototypes of brain injury suggest that RESV is an effective neuroprotective compound. Ability to enter the brain after a peripheral administration and no adverse effects on the brain or body are other features that are appealing for using this compound as a therapy for brain injury or neurodegenerative diseases. The goal of this review is to discuss the promise of RESV for treating acute seizures, preventing the acute seizure or status epilepticus induced development of chronic epilepsy, and easing the chronic epilepsy typified by spontaneous recurrent seizures and cognitive dysfunction. First, the various beneficial effects of RESV on the normal brain are discussed to provide a rationale for considering RESV treatment in the management of acute seizures and epilepsy. Next, the detrimental effects of acute seizures or status epilepticus on the hippocampus and the implications of post-status epilepticus changes in the hippocampus towards the occurrence of chronic epilepsy and cognitive dysfunction are summarized. The final segment evaluates studies that have used RESV as a neuroprotective compound against seizures, and proposes studies that are critically needed prior to the clinical application of RESV as a prophylaxis against the development of chronic epilepsy and cognitive dysfunction after an episode of status epilepticus or head injury. PMID:21554899
Greiner, Hansel M.; Tillema, Jan-Mendelt; Hallinan, Barbara E.; Holland, Katherine; Lee, Ki-Hyeong; Crone, Kerry R.
Medically refractory status epilepticus (RSE) causes high morbidity and mortality in children. There are no evidence-based guidelines for treatment. Epilepsy surgery is a treatment option for RSE. We describe a 9-year-old boy treated successfully for RSE with complete corpus callosotomy (CC). Epilepsy surgery should be considered for prolonged RSE. In the absence of evidence of focal epileptogenesis, complete corpus callosotomy may be effective in select cases. PMID:22326839
Bell, D. S.
The results of treatment of 25 patients admitted from psychiatric institutions indicate that diazepam is the drug of first choice in the treatment of status epilepticus. The dangers of treatment appeared to result from combined use with other drugs. Respiratory depression occurred in one patient and hypotension in five patients, all of whom had been given intramuscular phenobarbitone in addition to intravenous diazepam. The two serious cases of hypotension had also been given parenteral paraldehyde. PMID:4973764
Alford, Elizabeth L; Wheless, James W; Phelps, Stephanie J
Generalized convulsive status epilepticus (GCSE) is one of the most common neurologic emergencies and can be associated with significant morbidity and mortality if not treated promptly and aggressively. Management of GCSE is staged and generally involves the use of life support measures, identification and management of underlying causes, and rapid initiation of anticonvulsants. The purpose of this article is to review and evaluate published reports regarding the treatment of impending, established, refractory, and super-refractory GCSE in pediatric patients.
Induced Status Epilepticus Seizures John H. McDonough Kerry E. Van Shura Megan E. Lyman Claire G. Eisner Amelia Mazza Robert K. Kan Tsung...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Evaluation of ADD392124 for the delayed treatment of nerve agent-induced status epilepticus seizures 5b... status epilepticus seizures. We evaluated the ability of ADD392124 to control seizures induced by the nerve agent soman. Rats were exposed to a
Dillien, Philippe; Ferrao Santos, Susana; van Pesch, Vincent; Suin, Vanessa; Lamoral, Sophie; Hantson, Philippe
A 27-year-old previously healthy woman was admitted to the hospital with recurrent seizures. Status epilepticus developed that became refractory to third-line therapy with propofol and barbiturates. The patient had a very extensive diagnostic workup including autoimmune, viral and genetic investigations. A tentative immune therapy was proposed with high doses of steroids and plasma exchanges. Our patient had an inherited heterozygous single nucleotide variant in the sequence c.1280A>G [p.Lys427Arg] of the SMC3 gene that was insufficient to explain the seizures. Surprisingly, IgM antibodies against Japanese encephalitis virus were positive on the serum drawn 11 days after symptom onset, as detected by ELISA and the immunofluorescence antibody (IFA) technique. IgG antibodies were also positive using the IFA technique, but not with ELISA. The same investigations as well as the detection of the viral genome by the q-RT-PCR technique were negative on cerebrospinal fluid. Despite the suspicion of a viral infection, we concluded that our patient had a new-onset refractory status epilepticus of cryptogenic origin. Termination of the status epilepticus was obtained after 47 days, with a possible benefit from the introduction of ketamine. PMID:27462243
Hernandez-Lain, Aurelio; Hedley-Whyte, E Tessa; Hariri, Lida P; Molyneaux, Bradley; Nagle, Keith J; Cole, Andrew J; Kilbride, Ronan
To define the neuropathological findings of pulvinar degeneration seen in long duration status epilepticus. We review the clinical, radiologic, neurophysiologic, investigational and neuropathological findings on a 27 year old woman who died after 162 days of prolonged refractory status epilepticus. Continuous EEG monitoring confirmed recurrent uncontrolled seizure activity bilaterally and independently, most frequent in the right fronto-temporal region. Initial MRI of the brain was normal. Repeat study until on day 127 of admission showed advanced changes, with bilateral pulvinar T2/FLAIR hyperintensities. The autopsy revealed sharply defined, grey, soft, granular nodules in each medial pulvinar nucleus. Microscopically these consisted of sharply defined paucicellular areas with loss of neurons and myelin and with numerous macrophages in their centers, surrounded by reactive astrocytes with relatively spared of axons. The spinal cord at cervical and thoracic levels showed symmetric spongy vacuolation in the central part of the dorsal columns and lateral corticospinal tracts, with mild myelin loss, relatively preserved axons. The pathological lesions found in this case in thepulvinar are somewhat similar to the pathologic lesions described in Wernicke's encephalopathy. Those found in the spinal cord of our patient resemble characteristic features of B12 related subacute combined degeneration. Characteristic pulvinar degeneration may be found as an acquired phenomenon in prolonged refractory status epilepticus. We hypothesize that the neuropathological findings result from an excessive focal metabolic demand, secondary to neuronal network over activation in the setting of prolonged, frequent bi-temporal seizures. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Baysal Kirac, Leyla; Aydogdu, Ibrahim; Acarer, Ahmet; Alpaydin, Sezin; Bayam, Fatma Ece; Onbasi, Habibe; Bademkiran, Fikret
Myoclonic status epilepticus (MSE) is defined as prolonged period of myoclonic jerks that are correlated with epileptiform discharges on EEG. We here describe clinical features and video-EEG records of six adult patients with MSE who did not have a prior diagnosis of epilepsy. In four out of six patients, MSE was precipitated by drugs. Two out of four patients had chronic renal disease and received beta lactam group antibiotics. Two other patients, who described chronic pain, developed MSE while taking pregabalin. One patient who had dementia and family history of juvenile myoclonic epilepsy (JME) developed MSE one month after quetiapine was introduced. Another patient, who had a recent ischemic stroke, developed MSE due to an unknown reason. In these last two patients, an immediate triggering factor was not evident. Myoclonic status epilepticus ceased in five out of six patients after withdrawal of the drugs and/or intravenous antiepileptic treatment. Myoclonic status epilepticus is a rare event in patients without epilepsy. A correct diagnosis and prompt drug discontinuation may reverse this severe and life-threatening condition. PMID:25688046
Billington, Michael; Kandalaft, Osama R.; Aisiku, Imoigele P.
Seizures are a common presentation in the prehospital and emergency department setting and status epilepticus represents an emergency neurologic condition. The classification and various types of seizures are numerous. The objectives of this narrative literature review focuses on adult patients with a presentation of status epilepticus in the prehospital and emergency department setting. In summary, benzodiazepines remain the primary first line therapeutic agent in the management of status epilepticus, however, there are new agents that may be appropriate for the management of status epilepticus as second- and third-line pharmacological agents. PMID:27563928
Betjemann, John P; Josephson, S Andrew; Lowenstein, Daniel H; Burke, James F
Status epilepticus is a common neurologic emergency with significant associated morbidity, mortality, and health care costs, yet limited data exist detailing trends in status epilepticus-related hospitalizations and mortality. To examine trends in status epilepticus-related hospitalizations and mortality. We performed 2 retrospective serial cross-sectional studies including 408 304 status epilepticus-related hospital visits using generalizable national data from January 1, 1999, to December 31, 2010, from the Centers for Disease Control and Prevention and the Nationwide Inpatient Sample. Centers for Disease Control and Prevention death certificate data, using International Statistical Classification of Diseases, Tenth Revision, codes, were used to determine nonstandardized and age-standardized rates of status epilepticus as the underlying cause of death in the United States. Data from the Nationwide Inpatient Sample were used to estimate population-standardized status epilepticus-related hospitalization rates using International Statistical Classification of Diseases, Ninth Revision, codes. Status epilepticus-related hospitalizations were categorized by whether status epilepticus was the principal diagnosis, whether the patient was intubated, and by primary insurance type. Temporal trends were tested using Poisson regression and summarized with quarterly incident rate ratios. In 2010, status epilepticus was the reported underlying cause of death in 613 deaths (approximately 2 per 1 000 000 persons). Age-standardized status epilepticus-related mortality per 1 000 000 persons increased by only 5.6% (incident rate ratio, 1.004; 95% CI, 1.002-1.006) from 1.79 in 1999 to 1.89 in 2010, while population-standardized hospitalizations for status epilepticus per 100 000 persons increased by 56.4% (incident rate ratio, 1.013; 95% CI, 1.012-1.013) from 8.86 in 1999 to 13.86 in 2010. The largest increase (181.6%; incident rate ratio, 1.030; 95% CI, 1.029-1.030) was seen among
Sutter, Raoul; Kaplan, Peter W
There have been many attempts at defining the electroencephalography (EEG) characteristics of nonconvulsive status epilepticus (NCSE) without a universally accepted definition. This lack of consensus arises because the EEG expression of NCSE does not exist in isolation, but reflects status epilepticus under the variety of pathologic conditions that occur with age, cerebral development, encephalopathy, and epilepsy syndrome. Current NCSE definitions include "boundary conditions," in which electroencephalographic seizure activity occurs without apparent clinical seizures. Furthermore, what appears to one interpreter as status epilepticus, is not to another reader, reflecting the "art" of EEG interpretation. Seizures and epilepsy syndromes have undergone an evolution that has moved beyond a classification of focal or generalized conditions into a syndromic approach. It seems appropriate to make similar changes in the EEG analysis of the syndromes of NCSE. In effect, the literature on epilepsy classification has progressed to incorporate the different NCSE types with clinical descriptions, but the specific EEG evidence for these types is found largely in individual reports, and often by description only. NCSE classification of EEG patterns should derive from the aggregate of published EEG patterns in the respective clinical subtype, supported by an analysis of these EEG studies. The analysis that follows presents clinical descriptions and EEG patterns of NCSE in the neonatal period, infancy, childhood, adulthood, and late adulthood from a syndromic perspective based on age, encephalopathy, cerebral development, etiology, and syndrome. Proceeding from the proposed classification of status epilepticus syndromes in "Status epilepticus: its clinical features and treatment in children and adults" (published in 1994 by Cambridge University Press, New York), we have performed a systematic search for reports presenting EEG patterns of NCSE using the online medical search
Khawaja, Ayaz M; Vines, Brannon L; Miller, David W; Szaflarski, Jerzy P; Amara, Amy W
Glutamic acid decarboxylase antibodies (GAD-Abs) have been implicated in refractory epilepsy. The association with refractory status epilepticus in adults has been rarely described. We discuss our experience in managing three adult patients who presented with refractory status epilepticus associated with GAD-Abs. Case series with retrospective chart and literature review. Three patients without pre-existing epilepsy who presented to our institution with generalized seizures between 2013 and 2014 were identified. Seizures proved refractory to first and second-line therapies and persisted beyond 24 hours. Patient 1 was a 22-year-old female who had elevated serum GAD-Ab titres at 0.49 mmol/l (normal: <0.02) and was treated with multiple immuno- and chemotherapies, with eventual partial seizure control. Patient 2 was a 61-year-old black female whose serum GAD-Ab titre was 0.08 mmol/l. EEG showed persistent generalized periodic discharges despite maximized therapy with anticonvulsants but no immunotherapy, resulting in withdrawal of care and discharge to nursing home. Patient 3 was a 50-year-old black female whose serum GAD-Ab titre was 0.08 mmol/l, and was discovered to have pulmonary sarcoidosis. Treatment with steroids and intravenous immunoglobulin resulted in seizure resolution. Due to the responsiveness to immunotherapy, there may be an association between GAD-Abs and refractory seizures, including refractory status epilepticus. Causation cannot be established since GAD-Abs may be elevated secondary to concurrent autoimmune diseases or formed de novo in response to GAD antigen exposure by neuronal injury. Based on this report and available literature, there may be a role for immuno- and chemotherapy in the management of refractory status epilepticus associated with GAD-Abs.
Hong, Namgue; Choi, Yun-Sik; Kim, Seong Yun; Kim, Hee Jung
Status epilepticus is the most common serious neurological condition triggered by abnormal electrical activity, leading to severe and widespread cell loss in the brain. Lithium has been one of the main drugs used for the treatment of bipolar disorder for decades, and its anticonvulsant and neuroprotective properties have been described in several neurological disease models. However, the therapeutic mechanisms underlying lithium's actions remain poorly understood. The muscarinic receptor agonist pilocarpine is used to induce status epilepticus, which is followed by hippocampal damage. The present study was designed to investigate the effects of lithium post-treatment on seizure susceptibility and hippocampal neuropathological changes following pilocarpine-induced status epilepticus. Status epilepticus was induced by administration of pilocarpine hydrochloride (320 mg/kg, i.p.) in C57BL/6 mice at 8 weeks of age. Lithium (80 mg/kg, i.p.) was administered 15 minutes after the pilocarpine injection. After the lithium injection, status epilepticus onset time and mortality were recorded. Lithium significantly delayed the onset time of status epilepticus and reduced mortality compared to the vehicle-treated group. Moreover, lithium effectively blocked pilocarpine-induced neuronal death in the hippocampus as estimated by cresyl violet and Fluoro-Jade B staining. However, lithium did not reduce glial activation following pilocarpine-induced status epilepticus. These results suggest that lithium has a neuroprotective effect and would be useful in the treatment of neurological disorders, in particular status epilepticus.
Hong, Namgue; Choi, Yun-Sik; Kim, Seong Yun
Status epilepticus is the most common serious neurological condition triggered by abnormal electrical activity, leading to severe and widespread cell loss in the brain. Lithium has been one of the main drugs used for the treatment of bipolar disorder for decades, and its anticonvulsant and neuroprotective properties have been described in several neurological disease models. However, the therapeutic mechanisms underlying lithium's actions remain poorly understood. The muscarinic receptor agonist pilocarpine is used to induce status epilepticus, which is followed by hippocampal damage. The present study was designed to investigate the effects of lithium post-treatment on seizure susceptibility and hippocampal neuropathological changes following pilocarpine-induced status epilepticus. Status epilepticus was induced by administration of pilocarpine hydrochloride (320 mg/kg, i.p.) in C57BL/6 mice at 8 weeks of age. Lithium (80 mg/kg, i.p.) was administered 15 minutes after the pilocarpine injection. After the lithium injection, status epilepticus onset time and mortality were recorded. Lithium significantly delayed the onset time of status epilepticus and reduced mortality compared to the vehicle-treated group. Moreover, lithium effectively blocked pilocarpine-induced neuronal death in the hippocampus as estimated by cresyl violet and Fluoro-Jade B staining. However, lithium did not reduce glial activation following pilocarpine-induced status epilepticus. These results suggest that lithium has a neuroprotective effect and would be useful in the treatment of neurological disorders, in particular status epilepticus. PMID:28066149
Kohli, Sahil; Pasangulapati, Suresh Babu; Yoganathan, Sangeetha; Rynjah, Gideon Lyngsyun; Prabhakar, A T; Aaron, Sanjith; Alexander, Mathew; Mathew, Vivek
To determine the proportion of refractory status epilepticus (RSE) and super-RSE (SRSE) among patients with status epilepticus (SE) and to analyze RSE and non-RSE (NRSE) in terms of etiology and predictors for RSE. Patients were identified from discharge summaries database with keywords of SE and records of the portable electroencephalogram (EEG) machine from January 2011 to March 2016. Two hundred and eighteen events were included in the study with 114 (52.3%) males, bimodal age preponderance age <5 years 30%, and second peak in age 15-65 years 52.8%, preexisting seizures were present in 34.4% (n = 75). Nearly 77.1% had NRSE (n = 168) and 22.9% had RSE (n = 50). This included 17 patients with SRSE (n = 17, 7.8% of all SE). Central nervous system (CNS) infection was a single largest etiological group in SE (69/218, 31.7%). In RSE, autoimmune encephalitis (17/50) and CNS infection (13/50) were the largest groups. De novo seizures (P = 0.007), low sensorium at admission (P = 0.001), low albumin at admission (P = 0.002), and first EEG being abnormal (P = 0.001) were risk factors on bivariate analysis. An unfavorable status epilepticus severity score (STESS) was predictive for RSE (P = 0.001). On multivariate analysis, de novo seizures (P = 0.009) and abnormal EEG at admission (P = 0.03) were predictive for RSE. Fifty patients had RSE (22.9%), of which 17 went on to become SRSE (7.8%). Unfavorable STESS score was predictive for RSE on bivariate analysis. On multivariate analysis, de novo seizures and abnormal initial EEG were predictors of RSE.
Skinner, Holly J; Dubon-Murcia, Sofia A; Thompson, Arnold R; Medina, Marco T; Edwards, Jonathan C; Nicholas, Joyce S; Holden, Kenton R
Epidemiologic data on convulsive status epilepticus (CSE) is needed to develop preventative strategies. Epilepsy is one of the known risk factors for CSE. A systematic review of epidemiologic studies on status epilepticus (SE) completed in the United States and Europe reports that people with epilepsy account for less than 50% of cases of SE in all age groups. Less is known about the epidemiology of SE in developing countries including those in Central America. A high incidence of epilepsy, widespread non-adherence to anti-epileptic drugs (AED), and common use of complementary and alternative medicines have been shown in all ages in the developing country of Honduras, Central America. In 2003, an epidemiologic study of CSE in Honduran children demonstrated it is common and exhibits a long duration until onset of treatment. The etiologies, treatment, and outcomes of CSE in Honduran adults have not been thoroughly studied. This study is a consecutive case series of 31 adult patients presenting with CSE to the adult medicine emergency department of the tertiary care "Hospital Escuela" in the capital city Tegucigalpa, Honduras. The majority (77.4%) of patients had a prior history of epilepsy. Non-adherence to AED was the most common etiology of CSE (75.0%). The mortality rate in this pilot CSE study was 14.8%, which is similar to studies from industrialized countries where mortality from status epilepticus ranged from 7.6 to 22% for all age groups. However, this rate is concerning given that CSE from epilepsy and AED non-adherence generally carries a good prognosis. Improving AED adherence in this population appears to be the most effective approach in decreasing the rate, and possibly the mortality of Honduran adult CSE. 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Halawa, Eman F; Draz, Iman; Ahmed, Dalia; Shaheen, Hala A
Convulsive status epilepticus is a common neurologic emergency in pediatrics. We aimed to study the etiology, clinical features, and prognostic factors among pediatric patients with convulsive status epilepticus. Seventy patients were included in this cohort study from pediatric emergency department of the specialized Children Hospital of Cairo University. The outcome was evaluated using the Glasgow Outcome Score. Acute symptomatic etiology was the most common cause of convulsive status epilepticus. Refractory convulsive status epilepticus was observed more significantly in cases caused by acute symptomatic etiologies. The outcome was mortality in 26 (37.1%) patients, severe disability in 15 (21.4%), moderate disability in 17 (24.3%), and good recovery in 12 (17.1%) patients. The significant predictor of mortality was lower modified Glasgow Coma Scale score on admission, whereas lower modified Glasgow Coma Scale score on admission and refractory convulsive status epilepticus were the significant predictors for disability and mortality. © The Author(s) 2015.
Lehtimäki, Kai; Långsjö, Jaakko W; Ollikainen, Jyrki; Heinonen, Hanna; Möttönen, Timo; Tähtinen, Timo; Haapasalo, Joonas; Tenhunen, Jyrki; Katisko, Jani; Öhman, Juha; Peltola, Jukka
Super-refractory status epilepticus is a condition characterized by recurrence of status epilepticus despite use of deep general anesthesia, and it has high morbidity and mortality rates. We report a case of a 17-year-old boy with a prolonged super-refractory status epilepticus that eventually resolved after commencing deep brain stimulation of the centromedian nucleus of the thalamus. Later attempt to reduce stimulation parameters resulted in immediate relapse of status epilepticus, suggesting a pivotal role of deep brain stimulation in the treatment response. Deep brain stimulation may be a treatment option in super-refractory status epilepticus when other treatment options have failed. ANN NEUROL 2017;81:142-146. © 2016 American Neurological Association.
Carosella, Christopher M; Greiner, Hansel M; Byars, Anna W; Arthur, Todd M; Leach, James L; Turner, Michele; Holland, Katherine D; Mangano, Francesco T; Arya, Ravindra
Electrographic status epilepticus in slow sleep or continuous spike and waves during slow-wave sleep is an epileptic encephalopathy characterized by seizures, neurocognitive regression, and significant activation of epileptiform discharges during nonrapid eye movement sleep. There is no consensus on the diagnostic criteria and evidence-based optimal treatment algorithm for children with electrographic status epilepticus in slow sleep. We describe a 12-year-old girl with drug-resistant electrographic status epilepticus in slow wave sleep that was successfully treated with vagus nerve stimulation. Her clinical presentation, presurgical evaluation, decision-making, and course after vagus nerve stimulator implantation are described in detail. After vagus nerve stimulator implantation, the girl remained seizure free for more than a year, resolved the electrographic status epilepticus in slow sleep pattern on electroencephalography, and exhibited significant cognitive improvement. Vagus nerve stimulation may be considered for electrographic status epilepticus in slow sleep. Copyright © 2016 Elsevier Inc. All rights reserved.
Chaudhry, Saqib A.; Afzal, Mohammad Rauf; Rodriguez, Gustavo J.; Majidi, Shahram; Bundlie, Scott; Hassan, Ameer E.; Suri, M. Fareed K.; Qureshi, Adnan I.
Objective To determine the association between human immunodeficiency virus (HIV) infection and status epilepticus and compare the outcomes of patients with status epilepticus with or without underlying HIV infection. Methods Patients with primary diagnosis of status epilepticus (cases) and status asthmaticus (controls) were identified from the 2002–2009 Nationwide Inpatient Sample (NIS) which is representative of all admissions in the United States. We performed logistic regression analysis adjusting for age, gender, co-morbid conditions, including hypertension, diabetes mellitus (DM), renal failure, alcohol use, and opportunistic infections. We compared the in hospital outcomes among patients admitted with status epilepticus in strata defined by underlying HIV infection. Results The rate of concurrent status epilepticus and HIV has increased over the last 7 years in hospitalized patients with status epilepticus in United States (0.14%–0.27% p<0.0001). The HIV infection was significantly associated with status epilepticus (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.8–2.6; p<0.0001)) after adjusting for age, gender, opportunistic infections, and cardiovascular risk factors. The in-hospital mortality was significantly higher while discharge with none or minimal disability was significantly lower in status epilepticus patients with underlying HIV infection (17.5% vs. 9.9%, p<0.0001) and (50.4% vs. 63.3%, p<0.0001), respectively. Conclusions Our study suggests that there is a direct association between HIV infection and status epilepticus. The proportion of patients admitted with concurrent status epilepticus and HIV infections is increasing and such patients have higher rates of poor discharge outcomes. PMID:26301033
Chaudhry, Saqib A; Afzal, Mohammad Rauf; Rodriguez, Gustavo J; Majidi, Shahram; Bundlie, Scott; Hassan, Ameer E; Suri, M Fareed K; Qureshi, Adnan I
To determine the association between human immunodeficiency virus (HIV) infection and status epilepticus and compare the outcomes of patients with status epilepticus with or without underlying HIV infection. Patients with primary diagnosis of status epilepticus (cases) and status asthmaticus (controls) were identified from the 2002-2009 Nationwide Inpatient Sample (NIS) which is representative of all admissions in the United States. We performed logistic regression analysis adjusting for age, gender, co-morbid conditions, including hypertension, diabetes mellitus (DM), renal failure, alcohol use, and opportunistic infections. We compared the in hospital outcomes among patients admitted with status epilepticus in strata defined by underlying HIV infection. The rate of concurrent status epilepticus and HIV has increased over the last 7 years in hospitalized patients with status epilepticus in United States (0.14%-0.27% p<0.0001). The HIV infection was significantly associated with status epilepticus (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.8-2.6; p<0.0001)) after adjusting for age, gender, opportunistic infections, and cardiovascular risk factors. The in-hospital mortality was significantly higher while discharge with none or minimal disability was significantly lower in status epilepticus patients with underlying HIV infection (17.5% vs. 9.9%, p<0.0001) and (50.4% vs. 63.3%, p<0.0001), respectively. Our study suggests that there is a direct association between HIV infection and status epilepticus. The proportion of patients admitted with concurrent status epilepticus and HIV infections is increasing and such patients have higher rates of poor discharge outcomes.
Carmona-Aparicio, Liliana; Zavala-Tecuapetla, Cecilia; González-Trujano, María Eva; Sampieri, Aristides Iii; Montesinos-Correa, Hortencia; Granados-Rojas, Leticia; Floriano-Sánchez, Esaú; Coballase-Urrutía, Elvia; Cárdenas-Rodríguez, Noemí
The epileptic state, or status epilepticus (SE), is the most serious situation manifested by individuals with epilepsy, and SE events can lead to neuronal damage. An understanding of the molecular, biochemical and physiopathological mechanisms involved in this type of neurological disease will enable the identification of specific central targets, through which novel agents may act and be useful as SE therapies. Currently, studies have focused on the association between oxidative stress and SE, the most severe epileptic condition. A number of these studies have suggested the use of antioxidant compounds as alternative therapies or adjuvant treatments for the epileptic state.
Fjølner, Jesper; Søndergaard, Esben; Kampmann, Ulla; Nielsen, Søren
We report a case of life-threatening myxoedema presenting with hypothermia, hypotension, bradycardia, pericardial effusion and deep coma. The condition was complicated by prolonged status epilepticus. The optimal treatment strategy has been debated over the years and the literature is briefly reviewed. Treatment with l-thyroxine (LT4) monotherapy without initial loading dose and with no l-triiodothyronine (LT3) treatment was successful with full recovery after hospitalisation for more than a month. Myxoedema coma is a rare, reversible condition with a high mortality and should be considered as a differential diagnosis in medical emergencies. 2015 BMJ Publishing Group Ltd.
Carmona-Aparicio, Liliana; Zavala-Tecuapetla, Cecilia; González-Trujano, María Eva; Sampieri, Aristides Iii; Montesinos-Correa, Hortencia; Granados-Rojas, Leticia; Floriano-Sánchez, Esaú; Coballase-Urrutía, Elvia; Cárdenas-Rodríguez, Noemí
The epileptic state, or status epilepticus (SE), is the most serious situation manifested by individuals with epilepsy, and SE events can lead to neuronal damage. An understanding of the molecular, biochemical and physiopathological mechanisms involved in this type of neurological disease will enable the identification of specific central targets, through which novel agents may act and be useful as SE therapies. Currently, studies have focused on the association between oxidative stress and SE, the most severe epileptic condition. A number of these studies have suggested the use of antioxidant compounds as alternative therapies or adjuvant treatments for the epileptic state. PMID:27698680
Sasaki, Jun; Chegondi, Madhurandhar; Raszynski, Andre; Totapally, Balagangadhar R
Acute encephalitis in children is a life-threatening neurological emergency. However, little is reported about the outcome of this devastating illness in the United States. The authors retrospectively reviewed the charts of patients admitted to a regional pediatric intensive care unit with the diagnosis of acute encephalitis between 2006 and 2011. In 41 cases that met the inclusion criteria, the most common presenting symptoms were fever (65.9%), altered mental status (61%), and seizures (58.5%). Eight patients (19.5%) who presented with refractory status epilepticus had a longer median length of stay in the pediatric intensive care unit (46 vs. 4 days; P < .0001) and a significant worsening of Pediatric Cerebral Performance Category score on discharge by 2 or more points (odds ratio 20.38; 95% confidence interval, 2.89-143.52). All children survived to hospital discharge. In conclusion, children with acute encephalitis who present with refractory status epilepticus have a worse neurological outcome and a longer stay in the pediatric intensive care unit. © The Author(s) 2014.
Johnson, Emily L; Martinez, Nirma Carballido; Ritzl, Eva K
Refractory status epilepticus (RSE) is often treated with continuous intravenous medications with the goal of EEG burst suppression. Standard advice is to titrate medications to at least 10-s interburst intervals; however, this has not been shown to improve outcome. We examined EEG characteristics in patients treated with IV anesthetic therapy (IVAT) for RSE to determine which EEG characteristics were associated with successful lifting of IVAT (i.e., without recurrence of status epilepticus). We screened the clinical continuous EEG database for adult patients treated with IVAT for RSE (excluding patients with anoxic injury). We measured the length of bursts and interburst intervals for each patient, calculated EEG burst suppression ratios, and graded bursts for the amount of epileptiform activity. We compared these characteristics in successful versus unsuccessful IVAT lifting attempts. We included 17 successful and 20 unsuccessful lifting attempts in 19 patients (5 used as a holdout validation set). The interburst intervals, burst suppression ratios, and length of bursts did not differentiate successful and unsuccessful lifting attempts; the amount of epileptiform activity in bursts correlated with success or failure to wean IVAT (p = 0.008). Maximum burst amplitude <125 μV had 84.6 % sensitivity and 61.1 % specificity for predicting successful lifting. The length of interburst intervals and burst suppression did not predict successful termination of RSE in this small cohort. This may suggest that EEG characteristics, rather a strict interburst interval goal, could guide IVAT for RSE.
Valentín, Antonio; Nguyen, Huy Q; Skupenova, Alena M; Agirre-Arrizubieta, Zaloa; Jewell, Sharon; Mullatti, Nandini; Moran, Nicholas F; Richardson, Mark P; Selway, Richard P; Alarcón, Gonzalo
Refractory status epilepticus (RSE) is associated with high mortality. We report a potential treatment alternative. Deep brain stimulation (DBS) of the centromedian thalamic nuclei (CMN) can be effective in the treatment of RSE. Report of the evolution of RSE after DBS of the CMN in a 27-year-old man. In the course of an encephalopathy of unknown origin, and after a cardiac arrest, the patient developed RSE with myoclonic jerks and generalized tonic-clonic seizures. The EEG showed continuous generalized periodic epileptiform discharges (GPEDS). Five weeks after RSE onset, bilateral DBS of the CMN was started. This treatment was immediately followed by disappearance of tonic-clonic seizures and GPEDS, suggesting a resolution of RSE. The patient continued having multifocal myoclonic jerks, probably subcortical in origin, which resolved after 4 weeks. The patient remained clinically stable for 2 months in a persistent vegetative state. The remission of RSE, the abolition of GPEDS, and the patient survival suggest that DBS of the CMN may be efficacious in the treatment of refractory, generalized status epilepticus. Copyright © 2012 Elsevier Inc. All rights reserved.
Sort, Rune; Born, Alfred P; Pedersen, Karen N; Fonsmark, Lise; Uldall, Peter
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. A 3-year-old girl with RSE due to Hemiconvulsion-Hemiplegia Epilepsy syndrome. KD was instigated on day 6. Seizures stopped with ketosis on day 7. A 10-year-old boy rapidly developing RSE. After months a mitochondrial disorder was discovered. KD was tried twice with severe side-effects but no seizure control. 11-year-old healthy boy with RSE as FIRES. On KD seizures stopped for 24 h one day after reaching ketosis. He improved over 3-4 weeks. KD was efficient in two of three cases of RSE. The non-responder had severe side-effects and proved to have a mitochondrial disorder which is arguably a contraindication for KD. More studies are needed to prove efficacy of KD in RSE, to define optimal timing of KD and possible contraindications for KD in RSE. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Strzelczyk, A; Kortland, L-M; Knake, S; Rosenow, F
To determine whether stiripentol (STP) might be a treatment option in super-refractory status epilepticus (SRSE). Medical records of patients treated due to a status epilepticus in Marburg between January 2013 and June 2014 were reviewed for administration of STP. Primary outcome measures were resolution of SE after initiation of STP. Five adult patients were started with STP due to SRSE. The median age was 78 years (interquartile range [IQR] 11 years), and four patients were female. The median duration of SRSE before initiation of STP was 39 days (IQR 16 days), and the median number of anticonvulsants used before was 6 (IQR 1). SRSE ceased in three patients within 2-4 days after the start of STP. In two patients, SRSE continued after administration of STP and further escalation of anticonvulsant regimen. Both were switched eventually to supportive care only. None serious side effects were observed while on STP. Based on our presented cases and previous experimental animal data, STP may prove useful in treating super-refractory SE. Prospective trials are warranted to examine the efficacy of the STP in adults with refractory SE and to examine whether earlier treatment leads to better control of SE. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Wilcox, Karen S; Gee, James M; Gibbons, Meredith B; Tvrdik, Petr; White, John A
Temporal lobe epilepsy (TLE) is a devastating seizure disorder that is often caused by status epilepticus (SE). Temporal lobe epilepsy can be very difficult to control with currently available antiseizure drugs, and there are currently no disease-modifying therapies that can prevent the development of TLE in those patients who are at risk. While the functional changes that occur in neurons following SE and leading to TLE have been well studied, only recently has research attention turned to the role in epileptogenesis of astrocytes, the other major cell type of the brain. Given that epilepsy is a neural circuit disorder, innovative ways to evaluate the contributions that both neurons and astrocytes make to aberrant circuit activity will be critical for the understanding of the emergent network properties that result in seizures. Recently described approaches using genetically encoded calcium-indicating proteins can be used to image dynamic calcium transients, a marker of activity in both neurons and glial cells. It is anticipated that this work will lead to novel insights into the process of epileptogenesis at the network level and may identify disease-modifying therapeutic targets that have been missed because of a largely neurocentric view of seizure generation following SE. This article is part of a Special Issue entitled "Status Epilepticus".
Spindler, Meredith; Jacks, Lindsay M; Chen, Xi; Panageas, Katherine; DeAngelis, Lisa M; Avila, Edward K
Determine incidence, clinical presentation, electrographic correlates, and outcome of nonconvulsive status epilepticus (NCSE) in cancer patients on whom an EEG was performed. Retrospective review of 947 EEG reports on 658 patients in whom any type of EEG was performed at Memorial Sloan-Kettering Cancer Center (July 2006 to March 2008). Using the Epilepsy Research Foundation criteria, patients were classified as definite or probable NCSE. Medical records were reviewed for diagnosis, causes of NCSE, response to treatment, and outcome. Mortality was determined for patients with NCSE. Twenty-six episodes of NCSE were identified in 25 patients (25/658, 4%). Eleven patients had primary brain tumor, 12 patients systemic cancer, and two had both. At diagnostic EEG, 18 were awake, 3 were lethargic, and 5 patients were comatose. EEG revealed a seizure in 62% of the patients, periodic lateralized epileptiform discharges in 42%, and periodic epileptiform discharges in 7.7%. Neuroimaging revealed new intracranial pathology in 54% of the patients. Seventy-seven percent of the patients achieved control; 65% required ≥3 antiepileptic drugs, and 33% required intubation. Three patients died from NCSE. In our cohort, awake NCSE was more common than comatose NCSE. Treatment was successful in patients with heterogeneous central nervous system disease. EEG evaluation should be considered in patients with cancer because NCSE is treatable despite a high prevalence of structural brain disease. Nonconvulsive status epilepticus control did not always require intubation and burst suppression, but frequently required three or more antiepileptic drugs.
Suleiman, J; Brenner, T; Gill, D; Brilot, F; Antony, J; Vincent, A; Lang, B; Dale, R C
Voltage-gated potassium channel antibodies (VGKC Ab) are associated with limbic encephalitis and neuromyotonia in adults. There have been no systematic investigations in children to date. We looked for antibodies that are associated with CNS syndromes in adults including antibodies to VGKCs, NMDARs, glutamic acid decarboxylase (GAD), and glycine receptor (GlyR) in the stored acute serum from 10 children with unexplained encephalitis presenting with encephalopathy and status epilepticus. We also looked for antibodies to leucine-rich glioma-inactivated 1 (Lgi1) and contactin-associated protein-like 2 (Caspr2), which are now known to be tightly complexed with VGKCs in vivo. Sixty-nine pediatric controls were used for comparison. An elevated VGKC Ab (>100 pM) was detected in 4/10 patients with encephalitis compared to only 1/69 controls (p < 0.001). The outcome in the 4 VGKC Ab-positive patients with encephalitis was variable including good recovery (n = 1), cognitive impairment (n = 3), temporal lobe epilepsy (n = 2), and mesial temporal sclerosis (n = 1). No other antibodies were detected, including those to Lgi1 and Caspr2. Encephalitis associated with VGKC Ab occurs in children and presents with status epilepticus and focal epilepsy. These antibodies are not directed against Lgi1 or Caspr2.
The diagnosis and management of nonconvulsive status epilepticus (NCSE) pose special challenges in childhood. NCSE can be defined as a condition of ongoing or intermittent clinical epileptic activity without convulsions, for at least 30 minutes, with electroencephalographic evidence of seizures. NCSE accounts for approximately one-quarter of all cases of status epilepticus. NCSE should be suspected in children with epilepsy who undergo an otherwise inexplicable change in behavior and in children with recent onset change in speech, memory, school performance. NCSE can be observed in acute neurological injuries, specific childhood epilepsy syndromes, individuals with learning difficulties and other neurological conditions. NCSE is not uncommon in pediatric patients with an altered state of consciousness. NCSE in children is thought to be under-recognized. It is a highly heterogeneous clinical condition that is understudied in the pediatric population. Prompt recognition and treatment may be necessary to improve neurological outcome. Based on clinical semiology alone, diagnosis is difficult and requires emergent EEG. Management is often difficult, with highly variable response to treatment. Here I describe the diagnosis and management of NCSE in children.
Chen, Xiao-Qiao; Zhang, Wei-Na; Hu, Lin-Yan; Liu, Meng-Jia; Zou, Li-Ping
Epileptic encephalopathy with electrical status epilepticus during sleep is an age-related and self-limited disorder. The present study analyzed the etiology, demographics, and pathogenesis of patients with electrical status epilepticus during sleep to provide information on the diagnosis and therapy of this syndrome. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in patients admitted in Chinese People's Liberation Army General Hospital from 2009 to 2014 were retrospectively analyzed. Patients were classified into the genetic, structural-metabolic, and unknown groups according to the etiology. Demographics and clinical characteristics of all the patients were then analyzed and compared among groups. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in 75 patients mainly included benign childhood epilepsy with centrotemporal spikes, Landau-Kleffner syndrome, polymicrogyria, and migration disorders. Age at onset of epilepsy did not show a specific pattern, but age at onset of epileptic encephalopathy with electrical status epilepticus during sleep was concentrated at age 6-9 years. The mean age at onset of epilepsy in the genetic group was significantly older than that in the structural-metabolic group (P < 0.05). Age at onset of epileptic encephalopathy with electrical status epilepticus during sleep did not significantly differ between the two groups. Electrical status epilepticus during sleep is an epileptic encephalopathy related to brain development and presents an age-dependent occurrence. Copyright © 2016 Elsevier Inc. All rights reserved.
Shin, Hae W; O'Donovan, Cormac A; Boggs, Jane G; Grefe, Annette; Harper, Amy; Bell, William L; McCall, W Vaughn; Rosenquist, Peter
Status epilepticus is a life threatening condition with a high mortality rate in spite of aggressive treatment. There is little consensus on third and fourth line approaches in refractory cases. While electroconvulsive therapy (ECT) has been employed successfully as a treatment for refractory epilepsy and status epilepticus (SE) after exhausting conventional therapy, its use for pediatric patients is limited. We describe a 7-year-old pediatric case in which ECT was used successfully to treat medically refractory nonconvulsive status epilepticus (NCSE) without complete withdrawal of antiepileptic drugs (AED). Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Abend, Nicholas S.; Monk, Heather M.; Licht, Daniel J.; Dlugos, Dennis J.
Objective Intravenous (IV) levetiracetam (LEV) is approved for use in patients older than 16 years and may be useful in critically ill children, although there is little data available regarding pharmacokinetics. We aim to investigate the safety, an appropriate dosing, and efficacy of IV LEV in critically ill children. Design We describe a cohort of critically ill children who received IV LEV for status epilepticus, including refractory or nonconvulsive status, or acute repetitive seizures. Results There were no acute adverse effects noted. Children had temporary cessation of ongoing refractory status epilepticus, termination of ongoing nonconvulsive status epilepticus, cessation of acute repetitive seizures, or reduction in epileptiform discharges with clinical correlate. Conclusions IV LEV was effective in terminating status epilepticus or acute repetitive seizures and well tolerated in critically ill children. Further study is needed to elucidate the role of IV LEV in critically ill children. PMID:19325512
Wessels, T; Blaes, F; Röttger, C; Hügens, M; Hüge, S; Jauss, M
The most common neurologic manifestations of acute intermittent porphyria (AIP) are autonomic visceral neuropathy, peripheral motor neuropathy, and CNS dysfunctions including seizures and neuropsychiatric disturbances. In rare instances, however, AIP patients have presented with acute cortical blindness. We present a 20-year-old woman who suffered her first attack of AIP. Following 1 week of abdominal pain, she was transferred from a surgical department because of sudden visual loss and deterioration of consciousness. On admission, she developed several generalized seizures. Magnetic resonance imaging showed bilateral DWI lesions occipitally and in the left anterior circulation. Cerebrospinal fluid, MR angiography, and duplex ultrasound were normal. On the following day, sedation and intubation became necessary because of a generalized status epilepticus. Analysis of porphyrinogens in blood, urine and stool showed significantly elevated values. Intravenous therapy with häm-arginate was initiated and antiepileptic therapy was changed to gagabentine. Under this therapeutical regime she remained stable and extubation was possible 48 h later.
Epilepsy is part of the clinical phenotype in nearly 40% of children with mitochondrial disease, yet the underlying molecular mechanisms remain poorly understood. Energy depletion has been postulated as the cause of mitochondrial epilepsy, but if this were the case, then 100% of patients with mitochondrial disease would be expected to present with seizures. This review explores other potential disease mechanisms underlying mitochondrial epilepsy, including oxidative stress, impaired calcium homeostasis, immune dysfunction, and deficiency of vitamins, cofactors, reducing equivalents, and other metabolites. Different mechanisms are likely to predominate in different mitochondrial disorders, since mitochondrial function varies between neurons and astrocytes, between different types of neurons, and in different brain regions. Systematic studies in cell and animal models of mitochondrial disease are needed in order to develop effective therapies for mitochondrial epilepsy. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.
Molinero, Marco R; Holden, Kenton R; Rodriguez, Luis C; Collins, Julianne S; Samra, Jose A; Shinnar, Shlomo
Convulsive status epilepticus (SE) in children is an important public health problem, particularly in low-resource countries. A surveillance study was performed with consecutive enrollment of all children presenting with convulsive SE to Hospital Escuela Materno-Infantil Emergency Department in Tegucigalpa, Honduras over a 13-week period in 2003. In the 47 children with SE, the mean age was 4.5 years and the median seizure duration was 95 min. Mortality and morbidity were higher in children from rural locations, with all six deaths and three cases of new neurologic abnormalities occurring in rural children who had acute symptomatic SE. We conclude that childhood SE is common in the low-resource developing country of Honduras. Given the long delays in obtaining initial treatment in pediatric emergency facilities, availability of prehospital treatment may be of particular importance in this setting.
Beniczky, Sándor; Hirsch, Lawrence J; Kaplan, Peter W; Pressler, Ronit; Bauer, Gerhard; Aurlien, Harald; Brøgger, Jan C; Trinka, Eugen
The diagnosis of nonconvulsive status epilepticus (NCSE) relies largely on electroencephalography (EEG) findings. The lack of a unified EEG terminology, and of evidence-based EEG criteria, leads to varying criteria for and ability to diagnose NCSE. We propose a unified terminology and classification system for NCSE, using, as a template, the Standardised Computer-based Organised Reporting of EEG (SCORE). This approach integrates the terminology recently proposed for the rhythmic and periodic patterns in critically ill patients, the electroclinical classification of NCSE (type of NCSE) and the context for the pathologic conditions and age-related epilepsy syndromes. We propose flexible EEG criteria that employ the SCORE system to assemble a database for determining evidence-based EEG criteria for NCSE.
Brophy, Gretchen M; Bell, Rodney; Claassen, Jan; Alldredge, Brian; Bleck, Thomas P; Glauser, Tracy; Laroche, Suzette M; Riviello, James J; Shutter, Lori; Sperling, Michael R; Treiman, David M; Vespa, Paul M
Status epilepticus (SE) treatment strategies vary substantially from one institution to another due to the lack of data to support one treatment over another. To provide guidance for the acute treatment of SE in critically ill patients, the Neurocritical Care Society organized a writing committee to evaluate the literature and develop an evidence-based and expert consensus practice guideline. Literature searches were conducted using PubMed and studies meeting the criteria established by the writing committee were evaluated. Recommendations were developed based on the literature using standardized assessment methods from the American Heart Association and Grading of Recommendations Assessment, Development, and Evaluation systems, as well as expert opinion when sufficient data were lacking.
Beni, L; Constantini, S; Matoth, I; Pomeranz, S
A 14-year-old girl with closed head injury and a normal computerized tomographic scan underwent an electroencephalographic tracing that surprisingly revealed typical status epilepticus electrical activity. No episodes of motor clinical convulsions were observed from the moment of trauma throughout the admission period. Treatment with phenytoin caused a dramatic clinical improvement. Repeated electroencephalogram (EEG) 4 days later was within normal limits. Posttraumatic seizures are reported after head injury, yet, the issue of "invisible" or "subclinical" seizures associated with trauma is not discussed. In these cases EEG, (an uncommon examination in the early period after head injury) may be the only tool for proper diagnosis and treatment with anticonvulsants. This case report raises the question of the role of EEG in the unconscious patients who does not present with obvious convulsions. Clinical indications for performing EEG after head trauma without seizures are discussed.
Sutter, Raoul; Semmlack, Saskia; Kaplan, Peter W
Nonconvulsive status epilepticus (NCSE) is a state of continuous or repetitive seizures without convulsions. Owing to the nonspecific symptoms and considerable morbidity and mortality associated with NCSE, clinical research has focused on early diagnosis, risk stratification and seizure termination. The subtle symptoms and the necessity for electroencephalographic confirmation of seizures result in under-diagnosis with deleterious consequences. The introduction of continuous EEG to clinical practice, and the characterization of electrographic criteria have delineated a number of NCSE types that are associated with different prognoses in several clinical settings. Epidemiological studies have uncovered risk factors for NCSE; knowledge of these factors, together with particular clinical characteristics and EEG observations, enables tailored treatment. Despite these advances, NCSE can be refractory to antiepileptic drugs, necessitating further escalation of treatment. The presumptive escalation to anaesthetics, however, has recently been questioned owing to an association with increased mortality. This Review compiles epidemiological, clinical and diagnostic aspects of NCSE, and considers current treatment options and prognosis.
Cannon, Bryan C.; Ritter, Matthew J.; Schueler, Kerry E.
Propylene glycol (PG) is a solvent commonly used in medications that, while benign at low doses, may cause toxicity in adults and children at high doses. We describe a case and the physiologic sequelae of propylene glycol toxicity manifested in a critically ill adolescent male with refractory myoclonic status epilepticus aggressively treated with multiple PG-containing medications (lorazepam, phenobarbital, and pentobarbital)—all within accepted dosing guidelines and a total daily PG exposure previously recognized to be safe. Hemodynamic measurements by bedside echocardiography during clinical toxicity are also reported. Clinicians should have a high index of suspicion for propylene glycol toxicity in patients treated with PG-containing medications even when the total PG exposure is lower than currently accepted limits. PMID:28331645
Synowiec, Andrea S; Singh, Deepinder S; Yenugadhati, Vamsi; Valeriano, James P; Schramke, Carol J; Kelly, Kevin M
Refractory status epilepticus (RSE) occurs when status epilepticus (SE) fails to respond to appropriate therapy with typical antiepileptic drugs (AEDs). Animal studies have shown ketamine to be a highly efficacious agent in this setting, but very few case reports describe use of ketamine in human SE or RSE. We report a retrospective review of 11 patients who were treated for RSE with ketamine infusion in addition to other standard AEDs over a nine-year period. Data collection included age, gender, history of epilepsy, etiology of RSE, daily dose of ketamine, co-therapeutic agents, duration of seizures, treatment response, and disposition. RSE was successfully terminated in all 11 patients treated with ketamine. Dosing ranged from 0.45 mg/kg/h to 2.1 mg/kg/h based upon the preference of the treating clinician and response to therapy, with maximal daily doses ranging from 1392 mg to 4200 mg. Ketamine was the last AED used prior to resolution of RSE in 7/11 (64%) cases. In the remaining four cases, one other AED was added after ketamine infusion had begun. Time from ketamine initiation to seizure cessation ranged from 4 to 28 days (mean=9.8, SD=8.9). In 7/11 patients, RSE was resolved within one week of starting therapy. Administration of ketamine was uniformly associated with improvement in hemodynamic stability. Six of the seven patients (85%) who required vasopressors during early treatment for RSE were able to be weaned from vasopressors during ketamine infusion. No acute adverse effects were noted. These findings suggest that ketamine may be a safe and efficacious adjunctive agent in the treatment of RSE. Copyright © 2013 Elsevier B.V. All rights reserved.
Jayalakshmi, Sita; Vooturi, Sudhindra; Chepuru, Ramesh; Sahu, Sambit; Surath, Mohandas
Convulsive status epilepticus (CSE) is a common neurologic emergency in elderly people. The current study elaborates the clinical characteristics and outcome of CSE in elderly patients. Analysis of data of generalized CSE patients, aged 60 years and above admitted at the neurointensive care unit (NICU) was performed. The primary outcome for analysis was in-hospital mortality. The study population was divided into groups based on progression of CSE and mortality to analyze difference in study variables. Mortality of the group was analyzed using life tables. A total of 33 patients satisfied the inclusion criteria from medical records of 212 patients with CSE. Mean age of the study population was 67.0 ± 6.8 years; 69.7% were men. Acute symptomatic aetiology was the commonest cause of CSE (60.6%); nine (27.3%) patients progressed to refractory status epilepticus (RSE) of which five patients had prolonged RSE. The overall mortality was 18.2%. Complications of mechanical ventilation and mean age were higher in patients who died. Though vascular aetiology was the leading cause of CSE (39.3%), it was not associated with progression to RSE or mortality. Acute symptomatic aetiology accounted for five out of the six deaths in the entire cohort. Less than one-third of elderly patients with CSE progressed to RSE. Vascular aetiology, the leading cause of generalized CSE in elderly, was not associated with progression to RSE and mortality. Acute symptomatic aetiology was associated with high mortality. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Madžar, Dominik; Geyer, Anna; Knappe, Ruben U; Gollwitzer, Stephanie; Kuramatsu, Joji B; Gerner, Stefan T; Hamer, Hajo M; Huttner, Hagen B
The aim of the study was to identify factors influencing long-term outcome and to evaluate the prognostic power of the Status Epilepticus Severity Score (STESS) in refractory status epilepticus (RSE). We retrospectively extracted data on baseline characteristics, RSE details, and hospital course including complications from all patients treated for RSE in our institution between January 2001 and January 2013. Functional outcome was assessed using the modified Rankin Scale (mRS) and was defined as good when either RSE did not lead to functional decline or when the resulting mRS score was 2 or below. Seventy-one episodes in 65 patients were analyzed. The median follow-up time was 12 weeks (IQR 6-35), two patients were lost to follow-up. Poor functional long-term outcome was observed in 42/69 (60.9%) episodes. In-hospital mortality occurred in 13/71 (18.3%) episodes. Multivariable analysis revealed that STESS ≥ 3, longer RSE duration, and sepsis were independently related to poor functional long-term outcome. Receiver operating characteristics (ROC) curve analyses confirmed the cut-off dichotomization into STESS ≥ 3 and STESS < 3 for optimal discrimination between good and poor outcome (AUC = 0.671, p = 0.002, YI = 0.368, NPV = 0.607, PPV = 0.756) and revealed an RSE duration of 10 days as a significant cut-off point associated with outcome (AUC = 0.712, p = 0.012, YI = 0.310; NPV = 0.545, PPV = 0.750). In conclusion, STESS and RSE duration represent relevant scores and parameters impacting long-term outcome after RSE. A shorter RSE duration is associated with better outcome and, therefore, rapid and adequate treatment for seizure termination should be enforced.
Trinka, Eugen; Leitinger, Markus
Nonconvulsive status epilepticus (NCSE) is common in patients with coma with a prevalence between 5% and 48%. Patients in deep coma may exhibit epileptiform EEG patterns, such as generalized periodic spikes, and there is an ongoing debate about the relationship of these patterns and NCSE. The purposes of this review are (i) to discuss the various EEG patterns found in coma, its fluctuations, and transitions and (ii) to propose modified criteria for NCSE in coma. Classical coma patterns such as diffuse polymorphic delta activity, spindle coma, alpha/theta coma, low output voltage, or burst suppression do not reflect NCSE. Any ictal patterns with a typical spatiotemporal evolution or epileptiform discharges faster than 2.5 Hz in a comatose patient reflect nonconvulsive seizures or NCSE and should be treated. Generalized periodic diacharges or lateralized periodic discharges (GPDs/LPDs) with a frequency of less than 2.5 Hz or rhythmic discharges (RDs) faster than 0.5 Hz are the borderland of NCSE in coma. In these cases, at least one of the additional criteria is needed to diagnose NCSE (a) subtle clinical ictal phenomena, (b) typical spatiotemporal evolution, or (c) response to antiepileptic drug treatment. There is currently no consensus about how long these patterns must be present to qualify for NCSE, and the distinction from nonconvulsive seizures in patients with critical illness or in comatose patients seems arbitrary. The Salzburg Consensus Criteria for NCSE  have been modified according to the Standardized Terminology of the American Clinical Neurophysiology Society  and validated in three different cohorts, with a sensitivity of 97.2%, a specificity of 95.9%, and a diagnostic accuracy of 96.3% in patients with clinical signs of NCSE. Their diagnostic utility in different cohorts with patients in deep coma has to be studied in the future. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015. Published by Elsevier Inc.
Barrueto, Fermin; Furdyna, Peter M; Hoffman, Robert S; Hoffman, Robert J; Nelson, Lewis S
The following case report demonstrates the severe consequences of refractory convulsive status epilepticus from an unfamiliar imported toxin, tetramethylenedisulfotetramine (TETS), and the difficulties of identifying the offending agent. A previously healthy 15-month-old girl was found by her parents playing with a white rodenticide powder brought from China. Fifteen minutes later, the child developed generalized seizures and was brought to an Emergency Department (ED). Her initial fingerstick blood glucose was 108 mg/dL. In the ED, the child was intubated for status epilepticus. Despite aggressive therapy with lorazepam, phenobarbital, and pyridoxine, she had 4 h of intermittent generalized seizure activity. She was extubated on the third hospital day, but appeared to have absence seizures and cortical blindness. Continuous electroencephalogram monitoring, performed weeks later, revealed severe diffuse cerebral dysfunction with multiple epileptogenic foci. The child remains developmentally delayed and is on valproic acid therapy for seizure control. Translation of the Chinese package labeling did not clarify its contents. Tetramethylenedisulfotetramine was finally confirmed by gas chromatography-mass spectrometry (GC-MS) in this rodenticide product and then quantified against a TETS standard that was synthesized in our laboratory. Tetramethylenedisulfotetramine is grouped with other "cage convulsants," such as picrotoxin, since they have a similar intercalating cyclical molecular structure and cause seizures through non-competitive gamma-aminobutyric acid (GABA) antagonism. The oral lethal dose 50% (LD50) in humans is estimated to be as low as 100 microg/kg. Our patient has severe diffuse cerebral dysfunction likely secondary to prolonged seizure activity after exposure to TETS.
Zubcević, S; Buljina, A; Gavranović, M; Uzicanin, S; Catibusić, F
The clinical algorithm is a text format that is specially suited for presenting a sequence of clinical decisions, for teaching clinical decision making, and for guiding patient care. Clinical algorithms are compared as to their clinical usefulness with decision analysis. We have tried to make clinical algorithm for managing status epilepticus in children that can be applicable to our conditions. Most of the algorithms that are made on this subject include drugs and procedures that are not available at our hospital. We identified performance requirement, defined the set of problems to be solved as well as who would solve them, developed drafts in several versions and put them in the discussion with experts in this field. Algorithm was tested and revised and graphical acceptability was achieved. In the algorithm we tried to clearly define how the clinician should make the decision and to be provided with appropriate feedback. In one year period of experience in working we found this algorithm very useful in managing status epilepticus in children, as well as in teaching young doctors the specifities of algorithms and this specific issue. Their feedback is that they find that it provides the framework for facilitating thinking about clinical problems. Sometimes we hear objection that algorithms may not apply to a specific patient. This objection is based on misunderstanding how algorithms are used and should be corrected by a proper explanation of their use. We conclude that methods should be sought for writing clinical algorithms that represent expert consensus. A clinical algorithm can then be written for many areas of medical decision making that can be standardized. Medical practice would then be presented to students more effectively, accurately and understood better.
Liu, Gumei; Gu, Bin; He, Xiao-Ping; Joshi, Rasesh B.; Wackerle, Harold D.; Rodriguiz, Ramona Marie; Wetsel, William C.; McNamara, James O.
Summary Temporal lobe epilepsy is the most common and often devastating form of human epilepsy. The molecular mechanism underlying the development of temporal lobe epilepsy remains largely unknown. Emerging evidence suggests that activation of the BDNF receptor, TrkB, promotes epileptogenesis caused by status epilepticus. We investigated a mouse model in which a brief episode of status epilepticus results in chronic recurrent seizures, anxiety-like behavior, and destruction of hippocampal neurons. We used a chemical-genetic approach to selectively inhibit activation of TrkB. We demonstrate that inhibition of TrkB commencing after status epilepticus and continued for two weeks prevents recurrent seizures, ameliorates anxiety-like behavior, and limits loss of hippocampal neurons when tested weeks to months later. That transient inhibition commencing after status epilepticus can prevent these long-lasting devastating consequences establishes TrkB signaling as an attractive target for developing preventive treatments of epilepsy in humans. PMID:23790754
İşgüder, Rana; Güzel, Orkide; Ceylan, Gökhan; Yılmaz, Ünsal; Ağın, Hasan
Because of the lack of studies comparing the efficacy and safety of levetiracetam and valproate before the induction of general anesthesia in the treatment of convulsive refractory status epilepticus in children, we aimed to compare the effectiveness of these antiepileptic drugs in patients with convulsive status epilepticus admitted to the Pediatric Intensive Care Unit between 2011 and 2014. Forty-six (59%) of the 78 patients received levetiracetam, and 32 (41%) received valproate for the treatment of refractory status epilepticus. The response rate was not significantly different between the 2 groups. Although no adverse event was noted in patients who received levetiracetam, 4 (12.5%) patients in the valproate group experienced liver dysfunction (P = .025). According to our results, levetiracetam and valproate may be used in the treatment of refractory status epilepticus before the induction of general anesthesia. Levetiracetam appears as effective as valproate, and also safer. © The Author(s) 2016.
Henshall, David C; Engel, Tobias
There remains a need for more efficacious treatments for status epilepticus. Prolonged seizures result in the release of ATP from cells which activates the P2 class of ionotropic and metabotropic purinoceptors. The P2X receptors gate depolarizing sodium and calcium entry and are expressed by both neurons and glia throughout the brain, and a number of subtypes are upregulated after status epilepticus. Recent studies have explored the in vivo effects of targeting ATP-gated P2X receptors in preclinical models of status epilepticus, with particular focus on the P2X7 receptor (P2X7R). The P2X7R mediates microglial activation and the release of the proepileptogenic inflammatory cytokine interleukin 1β. The receptor may also directly modulate neurotransmission and gliotransmission and promote the recruitment of immune cells into brain parenchyma. Data from our group and collaborators show that status epilepticus produced by intraamygdala microinjection of kainic acid increases P2X7R expression in the hippocampus and neocortex of mice. Antagonism of the P2X7R in the model reduced seizure severity, microglial activation and interleukin 1β release, and neuronal injury. Coadministration of a P2X7R antagonist with a benzodiazepine also provided seizure suppression in a model of drug-refractory status epilepticus when either treatment alone was minimally effective. More recently, we showed that status epilepticus in immature rats is also reduced by P2X7R antagonism. Together, these findings suggest that P2X receptors may be novel targets for seizure control and interruption of neuroinflammation after status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.
Park, Kang Min; Kim, Sung Eun; Lee, Byung In; Kim, Hyung Chan; Yoon, Dae Young; Song, Hong Ki; Bae, Jong Seok
The purpose of this study is to identify the top 100-cited articles dedicated to epilepsy and status epilepticus published in journals from January, 1950 through February, 2016 that have made key contributions in the field. We performed a search of journals and selected the top 100-cited articles on epilepsy and status epilepticus, respectively, by utilizing the Institute for Scientific Information database available under the banner of the Web of Science. The top-cited articles on epilepsy and status epilepticus were all published in 24 journals, respectively. In both fields of epilepsy and status epilepticus, the most frequently cited journal was Epilepsia (26 articles on epilepsy and 19 articles on status epilepticus). The 100 most-cited articles in the field of both epilepsy and status epilepticus mainly originated from institutions in the United States of America. The articles on epilepsy included 25 laboratory studies, 15 pharmacotherapy studies, 13 general review studies, 12 surgery studies, 11 neuroimaging studies, eight epidemiology studies, eight neuropsychiatry studies, six genetic studies, and two electrophysiology studies, whereas 41 laboratory studies, 21 epidemiology studies, 16 pharmacotherapy studies, nine electrophysiology studies, nine general review studies, and four neuroimaging studies were included in the field of status epilepticus. We demonstrate that neuroimaging, genetics, and surgery are emerging topics in the field of epilepsy over the past decades. Moreover, we found that the majority of top-cited articles on epilepsy and status epilepticus originated from institutions in the United States of America and most were published in Epilepsia. Copyright © 2017 Elsevier Ltd. All rights reserved.
Nakamura, Kensuke; Inokuchi, Ryota; Daidoji, Hiroaki; Naraba, Hiromu; Sonoo, Tomohiro; Hashimoto, Hideki; Tokunaga, Kurato; Hiruma, Takahiro; Doi, Kent; Morimura, Naoto
Benzodiazepines are used as first-line treatments for status epilepticus. Fosphenytoin (FPHT) is recommended for second-line therapy; however, intravenous injection of levetiracetam (LEV) may also be effective against status epilepticus. Herein, we compared the efficacy and safety of LEV as a second-line treatment for status epilepticus with FPHT in Japanese patients.Patients with status epilepticus were selected from the database of the Emergency and Critical Care Center of Hitachi General Hospital. The subjects were patients whose status epilepticus was successfully stopped by diazepam, and in whom FPHT or LEV was administered after diazepam. As LEV injections recently became clinically available in Japan, the choice of drug was determined by the treatment period. Thus, 21 patients who were intravenously injected with LEV as a second-line therapy and 42 matched patients (historical controls) who were treated with FPHT (1:2) were selected.The subjects had a mean age of 64.0 ± 2.2 years, and included 48 males and 15 females. The status epilepticus control rates of the FPHT and LEV groups did not differ significantly (81.0% [34/42] vs 85.1% [18/21], respectively; P = .69). As for serious adverse events, a reduction in blood pressure was observed in the FPHT group, but not in the LEV group. The oral anticonvulsant switching rates of the 2 groups were similar, but the same-drug switching rates of the FPHT and LEV groups were 8.1% and 77.8%, respectively.The efficacy of intravenous LEV injections after status epilepticus was equivalent to that of FPHT, and the incidence of adverse events was lower in the LEV group. LEV is effective and safe at preventing recurrent seizures after status epilepticus following benzodiazepine treatment.
Duffy, B A; Chun, K P; Ma, D; Lythgoe, M F; Scott, R C
Anti-inflammatory therapies are the current most plausible drug candidates for anti-epileptogenesis and neuroprotection following prolonged seizures. Given that vasogenic edema is widely considered to be detrimental for outcome following status epilepticus, the anti-inflammatory agent dexamethasone is sometimes used in clinic for alleviating cerebral edema. In this study we perform longitudinal magnetic resonance imaging in order to assess the contribution of dexamethasone on cerebral edema and subsequent neuroprotection following status epilepticus. Lithium-pilocarpine was used to induce status epilepticus in rats. Following status epilepticus, rats were either post-treated with saline or with dexamethasone sodium phosphate (10mg/kg or 2mg/kg). Brain edema was assessed by means of magnetic resonance imaging (T2 relaxometry) and hippocampal volumetry was used as a marker of neuronal injury. T2 relaxometry was performed prior to, 48 h and 96 h following status epilepticus. Volume measurements were performed between 18 and 21 days after status epilepticus. Unexpectedly, cerebral edema was worse in rats that were treated with dexamethasone compared to controls. Furthermore, dexamethasone treated rats had lower hippocampal volumes compared to controls 3 weeks after the initial insult. The T2 measurements at 2 days and 4 days in the hippocampus correlated with hippocampal volumes at 3 weeks. Finally, the mortality rate in the first week following status epilepticus increased from 14% in untreated rats to 33% and 46% in rats treated with 2mg/kg and 10mg/kg dexamethasone respectively. These findings suggest that dexamethasone can exacerbate the acute cerebral edema and brain injury associated with status epilepticus.
Lui, Hoi Ki Kate; Hui, Kwok Fai; Fong, Wing Chi; Ip, Chun Tak; Lui, Hiu Tung Colin
To identify predictors of poor clinical outcome in patients presenting to the intensive care units with status epilepticus (SE), in particular for patients presenting with de novo status epileptics. A retrospective review was performed on patients admitted to the intensive care units with status epilepticus in two hospitals in Hong Kong over an 11-year period from 2003 to 2013. A total of 87 SE cases were analyzed. The mean age of patients was 49.3 years (SD 14.9 years). Eighteen subjects (20.7%) had breakthrough seizure, which was the most common etiology for the status epilepticus episodes. Seventy-eight subjects (89.7%) had convulsive status epilepticus (CSE) and 9 subjects (10.3%) had non-convulsive status epilepticus (NCSE) on presentation. The 30-day mortality rate of all subjects was 18.4%. Non-convulsive status epilepticus was more common in patients with de novo status epilepticus when compared to those with existing history of epilepsy (15.5% Vs. 0%, p=0.03). Patients with de novo status epilepticus were older (52 Vs 43, p=0.009). De novo status epilepticus was associated with longer status duration (median 2.5 days, IQR 5 days), longer ICU stay (median 7.5 days, IQR 9 days) and poorer outcome (OR 4.15, 95% CI 1.53-11.2). For patients presenting to intensive care units with status epilepticus, those with de novo status epileptics were older and were more likely to develop non-convulsive status epilepticus. De novo status epilepticus was associated with poorer outcome. Continuous EEG monitoring would help identifying NCSE and potentially help improving clinical outcomes. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Liang, Zhaoliang; Gao, Fei; Wang, Fajun; Wang, Xiaochen; Song, Xinyu; Liu, Kejing; Zhan, Ren-Zhi
Enhanced neurogenesis in the dentate gyrus of the hippocampus following seizure activity, especially status epilepticus, is associated with ectopic residence and aberrant integration of newborn granule cells. Hilar ectopic granule cells may be detrimental to the stability of dentate circuitry by means of their electrophysiological properties and synaptic connectivity. We hypothesized that status epilepticus also increases ectopic granule cells in the molecular layer. Status epilepticus was induced in male Sprague-Dawley rats by intraperitoneal injection of pilocarpine. Immunostaining showed that many doublecortin-positive cells were present in the molecular layer and the hilus 7 days after the induction of status epilepticus. At least 10 weeks after status epilepticus, the estimated number of cells positive for both prospero homeobox protein 1 and neuron-specific nuclear protein in the hilus was significantly increased. A similar trend was also found in the molecular layer. These findings indicate that status epilepticus can increase the numbers of mature and ectopic newborn granule cells in the molecular layer. PMID:25206705
Dunleavy, Mark; Schindler, Clara K; Shinoda, Sachiko; Crilly, Shane; Henshall, David C
Status epilepticus in the adult brain invariably causes an increase in hippocampal neurogenesis and the appearance of ectopic cells and this has been implicated as a causal factor in epileptogenesis. The effect of status epilepticus on neurogenesis in the developing brain is less well characterized and models of early-life seizures typically do not reproduce the hippocampal damage common to human mesial temporal sclerosis. We recently reported that evoking status epilepticus by intra-amygdala microinjection of kainic acid in post-natal (P) day 10 rats caused substantial acute neuronal death within the ipsilateral hippocampus and rats later developed unilateral hippocampal sclerosis and spontaneous recurrent seizures. Here, we examined the expression of a selection of genes associated with neurogenesis and assessed neurogenic function in this model. Protein levels of several markers of neurogenesis including polysialic acid neural cell adhesion molecule, neuroD and doublecortin were reduced in the hippocampus three days after status epilepticus in P10 rats. In contrast, protein levels of neurogenesis markers were similar to control in rats at P55. Pulse-chase experiments using thymidine analogues suggested there was a reduction in new neurons at 72 h after status epilepticus in P10 rats, whereas numbers of new neurons labelled in epileptic rats at P55 with hippocampal sclerosis were similar to controls. The present study suggests that status epilepticus in the immature brain suppresses neurogenesis but the neurogenic potential is retained in animals that later develop hippocampal sclerosis. PMID:25755841
George, Pravin; Nattanmai, Premkumar; Ahrens, Christine; Hantus, Stephen; Sarwal, Aarti
Introduction. Status epilepticus is associated with neuronal breakdown. Radiological sequelae of status epilepticus include diffusion weighted abnormalities and T2/FLAIR cortical hyperintensities corresponding to the epileptogenic cortex. However, progressive generalized cerebral atrophy from status epilepticus is underrecognized and may be related to neuronal death. We present here a case of diffuse cerebral atrophy that developed during the course of super refractory status epilepticus management despite prolonged barbiturate coma. Methods. Case report and review of the literature. Case. A 19-year-old male with a prior history of epilepsy presented with focal clonic seizures. His seizures were refractory to multiple anticonvulsants and eventually required pentobarbital coma for 62 days and midazolam coma for 33 days. Serial brain magnetic resonance imaging (MRI) showed development of cerebral atrophy at 31 days after admission to our facility and progression of the atrophy at 136 days after admission. Conclusion. This case highlights the development and progression of generalized cerebral atrophy in super refractory status epilepticus. The cerebral atrophy was noticeable at 31 days after admission at our facility which emphasizes the urgency of definitive treatment in patients who present with super refractory status epilepticus. Further research into direct effects of therapeutic coma is warranted. PMID:28182114
Ferguson, Matthew; Bianchi, Matt T.; Sutter, Raoul; Rosenthal, Eric S.; Cash, Sydney S.; Kaplan, Peter W.
Objective To address the question: does non-convulsive status epilepticus warrant the same aggressive treatment as convulsive status epilepticus? Method We used a decision model to evaluate the risks and benefits of treating non-convulsive status epilepticus with intravenous anesthetics and ICU-level aggressive care. We investigated how the decision to use aggressive versus non-aggressive management for non-convulsive status epilepticus impacts expected patient outcome for four etiologies: absence epilepsy, discontinued antiepileptic drugs, intraparenchymal hemorrhage, and hypoxic ischemic encephalopathy. Each etiology was defined by distinct values for five key parameters: baseline mortality rate of the inciting etiology; efficacy of non-aggressive treatment in gaining control of seizures; the relative contribution of seizures to overall mortality; the degree of excess disability expected in the case of delayed seizure control; and the mortality risk of aggressive treatment. Results Non-aggressive treatment was favored for etiologies with low morbidity and mortality such as absence epilepsy and discontinued antiepileptic drugs. The risk of aggressive treatment was only warranted in etiologies where there was significant risk of seizure-induced neurologic damage. In the case of post-anoxic status epilepticus, expected outcomes were poor regardless of the treatment chosen. The favored strategy in each case was determined by strong interactions of all five model parameters. Conclusions Determination of the optimal management approach to non-convulsive status epilepticus is complex and is ultimately determined by the inciting etiology. PMID:23065689
Tasker, Robert C; Vitali, Sally H
To discuss the use of continuous infusions, general anesthesia, hypothermia, and ketogenic diet as treatment for uncontrolled status epilepticus in pediatric patients. Recent studies demonstrate that clinical practitioners have a hierarchy in approach in controlling refractory status epilepticus (RSE) and super-refractory status epilepticus in children. In the acute setting of RSE, midazolam achieves clinical seizure control at a mean of 41 min after starting an infusion. When midazolam has failed to control RSE, the evidence points to barbiturate anesthesia as the next frequently used option. When both midazolam and barbiturates have failed, use of isoflurane or ketamine anesthesia has been tried at a mean of 10 days after RSE onset, although the studies are largely anecdotal. Increasingly, the use of therapeutic hypothermia or ketogenic diet is described as a strategy for super-refractory status epilepticus, and better evidence for their use may become available from ongoing randomized studies. Uncontrolled episodes of status epilepticus require intensive care treatment and the literature describes a common pathway of care used by many. However, cases of truly refractory and super-refractory status epilepticus are seen infrequently at any given institution. One strategy to improve the quality of evidence is to develop prospective, national and multinational case registries to determine the range of presentations and causes, efficacy of treatments, and clinical outcomes.
Basha, Maysaa Merhi; Suchdev, Kushak; Dhakar, Monica; Kupsky, William J; Mittal, Sandeep; Shah, Aashit K
To identify the role of acute surgical intervention in the treatment of refractory status epilepticus (RSE). Retrospective review of consecutive patients who underwent epilepsy surgery from 2006 to 2015 was done to identify cases where acute surgical intervention was employed for the treatment of RSE. In addition, the adult and pediatric RSE literature was reviewed for reports of surgical treatment of RSE. Nine patients, aged 20-68 years, with various etiologies were identified to have undergone acute surgical resection for the treatment of RSE, aided by electrocorticography. Patients required aggressive medical therapy with antiepileptic drugs and intravenous anesthetic drugs for 10-54 days and underwent extensive neurodiagnostic testing prior to resective surgery. Eight out of nine patients survived and five patients were seizure-free at the last follow-up. The literature revealed 13 adult and 48 pediatric cases where adequate historical detail was available for review and comparison. We present the largest cohort of consecutive adult patients who underwent resective surgery in the setting of RSE. We also reveal that surgery can be efficacious in aborting status and in some can lead to long-term seizure freedom. Acute surgical intervention is a viable option in prolonged RSE and proper evaluation for such intervention should be conducted, although the timing and type of surgical intervention remain poorly defined.
Moseley, Brian D; Degiorgio, Christopher M
Refractory status epilepticus (RSE) is a neurologic emergency associated with significant morbidity and mortality. Alternative therapies are needed for patients who do not respond to more traditional therapies for RSE. We report on a patient with RSE treated with external trigeminal nerve stimulation (eTNS). On admission, the patient was experiencing consecutive focal dyscognitive seizures with secondary generalization without recovery in between. His seizures remained refractory to multiple therapies, including IV lorazepam, valproic acid, levetiracetam, phenobarbital, and midazolam. Although a burst suppression pattern was achieved with a continuous pentobarbital infusion, seizures returned following attempts to taper it. Given his beneficial response to eTNS during a previous clinical trial, eTNS was initiated. Four days after starting eTNS, the pentobarbital infusion was finally weaned, and his EEG revealed no further seizures. The patient's mental status improved and he was ultimately discharged with only moderately severe disability. Our case demonstrates that eTNS may have antiseizure effects in RSE. Given our patient's quick response, such benefit may have arisen from EEG-desynchronization. If confirmed in larger studies, eTNS could one day be considered along with other adjuvant treatments for RSE.
Mysore, Channaiah Srikanth; Zabad, Rana; Bertoni, John
Objective. We are reporting two cases: a patient with steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) and another patient with secondary progressive multiple sclerosis (SPMS), both presenting with altered mental status (AMS) and later diagnosed with nonconvulsive atypical absence status epilepticus (AS), with atypical EEG changes. Methods. A report of two cases. Results. A patient with history of SREAT and the other with SPMS had multiple admissions due to AMS. For both, EEG revealed the presence of a high voltage generalized sharply contoured theta activity. A diagnosis of NCSE with clinical features of AS was made based on both clinical and EEG features. There was significant clinical and electrographic improvement with administration of levetiracetam for both patients in addition to sodium valproate and Solumedrol for the SREAT patient. Both patients continued to be seizure free on follow-up few months later. Conclusions. This is a report of two cases of atypical AS, with atypical EEG, in patients with different neurological conditions. Prompt clinical and EEG recovery occurred following appropriate medical treatment. We think that this condition might be underreported and could significantly benefit from prompt treatment when appropriately diagnosed. PMID:28203468
Henshall, David C.; Diaz-Hernandez, Miguel; Miras-Portugal, M. Teresa; Engel, Tobias
Prolonged seizures are amongst the most common neurological emergencies. Status epilepticus is a state of continuous seizures that is life-threatening and prompt termination of status epilepticus is critical to protect the brain from permanent damage. Frontline treatment comprises parenteral administration of anticonvulsants such as lorazepam that facilitate γ-amino butyric acid (GABA) transmission. Because status epilepticus can become refractory to anticonvulsants in a significant proportion of patients, drugs which act on different neurotransmitter systems may represent potential adjunctive treatments. P2X receptors are a class of ligand-gated ion channel activated by ATP that contributes to neuro- and glio-transmission. P2X receptors are expressed by both neurons and glia in various brain regions, including the hippocampus. Electrophysiology, pharmacology and genetic studies suggest certain P2X receptors are activated during pathologic brain activity. Expression of several members of the family including P2X2, P2X4, and P2X7 receptors has been reported to be altered in the hippocampus following status epilepticus. Recent studies have shown that ligands of the P2X7 receptor can have potent effects on seizure severity during status epilepticus and mice lacking this receptor display altered seizures in response to chemoconvulsants. Antagonists of the P2X7 receptor also modulate neuronal death, microglial responses and neuroinflammatory signaling. Recent work also found altered neuronal injury and inflammation after status epilepticus in mice lacking the P2X4 receptor. In summary, members of the P2X receptor family may serve important roles in the pathophysiology of status epilepticus and represent novel targets for seizure control and neuroprotection. PMID:24324404
Hortigüela-Saeta, M Montesclaros; Conejo-Moreno, David; Gutiérrez-Moreno, Miriam; Gómez-Saiz, Luna
Status epilepticus is defined as either recurring seizures without regaining consciousness between them or one single seizure lasting more than 30 minutes. To perform a descriptive analysis of the most relevant data on the patients with status epilepticus who were admitted to a paediatric intensive care unit (PICU) and to review the risk factors associated to status epilepticus with a poor prognosis. A study was conducted of the main variables of the patients with status epilepticus hospitalised in the PICU of a tertiary hospital over a period of six years. Data were collected on a total of 68 patients (55.9% males), the mean age being 3.7 years. The most frequent signs and symptoms were generalised tonic-clonic seizures (50%). The mean duration of the status epilepticus was 51.44 minutes. The mean number of antiepileptic drugs used to stem the seizures was 3.21 and the mean number of drugs used prior to admission to the PICU was 2.37. The most commonly used first choice drug was diazepam (83.8%) administered rectally (75%), followed by intravenous diazepam (52.9%) in second place and phenytoin was the most frequently used drug as the third choice. The most usual cause of status epilepticus was having previously suffered from epilepsy (33.9%), and Dravet's syndrome was the most frequent epileptic causation. Treatment of status epilepticus is complex and requires multidisciplinary and personalised management. Protocols and clinical guidelines need to be drawn up and reviewed to achieve an adequate management of these patients.
Abend, Nicholas S; Wagenman, Katherine L; Blake, Taylor P; Schultheis, Maria T; Radcliffe, Jerilynn; Berg, Robert A; Topjian, Alexis A; Dlugos, Dennis J
Electrographic seizures (ESs) and electrographic status epilepticus (ESE) are common in children with acute neurologic conditions in pediatric intensive care units (PICUs), and ESE is associated with worse functional and quality-of-life outcomes. As an exploratory study, we aimed to determine if ESE was associated with worse outcomes using more detailed neurobehavioral measures. Three hundred children with an acute neurologic condition and altered mental status underwent clinically indicated EEG monitoring and were enrolled in a prospective observational study. We obtained follow-up data from subjects who were neurodevelopmentally normal prior to PICU admission. We evaluated for associations between ESE and adaptive behavior (Adaptive Behavior Assessment System-II, ABAS-II), behavioral and emotional problems (Child Behavior Checklist, CBCL), and executive function (Behavior Rating Inventory of Executive Function, BRIEF) using linear regression analyses. A p-value of <0.05 was considered significant. One hundred thirty-seven of 300 subjects were neurodevelopmentally normal prior to PICU admission. We obtained follow-up data from 36 subjects for the CBCL, 32 subjects for the ABAS-II, and 20 subjects for the BRIEF. The median duration from admission to follow-up was 2.6 years (IQR: 1.2-3.8). There were no differences in the acute care variables (age, sex, mental status category, intubation status, paralysis status, acute neurologic diagnosis category, seizure category, EEG background category, or short-term outcome) between subjects with and without follow-up data for any of the outcome measures. On univariate analysis, significant differences were not identified for CBCL total problem (ES coefficient: -4.1, p = 0.48; ESE coefficient: 8.9, p = 0.13) or BRIEF global executive function (ES coefficient: 2.1, p = 0.78; ESE coefficient: 14.1, p = 0.06) scores, although there were trends toward worse scores in subjects with ESE. On univariate analysis, ESs were not
Ylikotila, Pauli; Ketola, Raimo A; Timonen, Susanna; Malm, Heli; Ruuskanen, Jori O
Cerebral venous thrombosis (CVT) is an uncommon cause of stroke, accounting to less than 1% of all strokes. We describe a pregnant woman with a massive CVT in early pregnancy, complicated by status epilepticus. The mother was treated with levetiracetam, lacosamide, and enoxaparin throughout pregnancy. A male infant was born on pregnancy week 36, weighing 2.2kg. Both levetiracetam and and lacosamide were present in cord blood in levels similar to those in maternal blood. The infant was partially breast-fed and experienced poor feeding and sleepiness, starting to resolve after two first weeks. Milk samples were drawn 5 days after the delivery and a blood sample from the infant 3 days later. Lacosamide level in milk was low, resulting in an estimated relative infant dose of 1.8% of the maternal weight-adjusted daily dose in a fully breast-fed infant. This is the first case describing lacosamide use during pregnancy and lactation.
Gaete, Germán; Velásquez, Álvaro
The differential diagnosis of non-convulsive status epilepticus (NCSE) is often complex due to a wide clinical variability of its presentation, including psychiatric manifestations. We report a 68 years old male with a history of depression treated with venlafaxine, mirtazapine, quetiapine and risperidone, presenting in the emergency room with confusion and generalized rigidity. A brain CT scan did not show lesions. A neuroleptic syndrome was initially suspected. At the third day the obtundation worsened and an electroencephalogram (EEG) was performed, which showed epileptiform abnormalities. Treatment with valproic acid resulted in disappearance of such abnormalities. After three weeks of mechanical ventilation, the patient was extubated and remained lucid and partially orientated in time and space.
Rajasekaran, Karthik; Zanelli, Santina A.; Goodkin, Howard P
Status epilepticus (SE) is the most common neurological emergency of childhood. Experimental models parallel several clinical features of SE including: (1) treatment is complicated by an increasing probability that benzodiazepines will fail with increasing seizure duration and (2) outcome varies with age and etiology. Studies using these models demonstrated that the activity-dependent trafficking of GABAA receptors contributes, in part, to the progressive decline in GABA-mediated inhibition and the failure of the benzodiazepines. Furthermore, laboratory studies have provided evidence that age and inciting stimulus interact to determine the neuronal circuits activated during SE (i.e. functional anatomy), and that differences in functional anatomy can partially account for variations in SE outcome. Future laboratory studies are likely to provide an additional understanding of the cellular and molecular mechanisms that underlie SE and its consequences. Such studies are necessary in the development of rational emergent therapy for SE and its long term outcomes. PMID:20727481
Fujikawa, D.G.; Dwyer, B.E.; Lake, R.R.; Wasterlain, C.G.
The effect of bicuculline-induced status epilepticus (SE) on local cerebral metabolic rates for glucose (LCMRglc) was studied in 2-wk-old ketamine-anesthetized marmoset monkeys, using the 2-(/sup 14/C)-deoxy-D-glucose autoradiographical technique. To estimate LCMRglc in cerebral cortex and thalamus during SE, the lumped constant (LC) for 2-deoxy-D-glucose (2-DG) and the rate constants for 2-DG and glucose were calculated for these regions. The control LC was 0.43 in frontoparietal cortex, 0.51 in temporal cortex, and 0.50 in thalamus; it increased to 1.07 in frontoparietal cortex, 1.13 in temporal cortex, and 1.25 in thalamus after 30 min of seizures. With control LC values, LCMRglc in frontoparietal cortex, temporal cortex, and dorsomedial thalamus appeared to increase four to sixfold. With seizure LC values, LCMRglc increased 1.5- to 2-fold and only in cortex. During 45-min seizures, LCMRglc in cortex and thalamus probably increases 4- to 6-fold initially and later falls to the 1.5- to 2-fold level as tissue glucose concentrations decrease. Together with our previous results demonstrating depletion of high-energy phosphates and glucose in these regions, the data suggest that energy demands exceed glucose supply. The long-term effects of these metabolic changes on the developing brain remain to be determined.
Suarez-de-la-Rica, A; Hernández-Gancedo, C; López-Tofiño, A; Maseda, E; Gilsanz, F
Neurotoxicity caused by cefepime may occur predominantly in patients with impaired renal function. A case of a cefepime-induced non-convulsive status epilepticus (NCSE) is presented. A 65-year-old woman suffered a severe NCSE due to cefepime in the presence of acute renal failure, requiring coma induction with sodium thiopental. A serious interaction between valproic acid (VPA) and meropenem was also produced after changing cefepime to meropenem. Continuous veno-venous haemofiltration was employed to improve cefepime clearance, and the patient progressively regained her previous mental condition. In conclusion, the cefepime dose must be adjusted according to renal function in order to avoid toxicity in patients with renal failure. Electroencephalogram should be considered in cases of acute confusional state in patients receiving cefepime, to achieve early detection of NCSE. Continuous renal replacement therapy may be successfully employed in severe cases in order to accelerate cefepime removal. Likewise, meropenem should not be used concomitantly with VPA. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.
Status epilepticus (SE) is one of the most frequent neurological emergencies with an incidence of 20/100,000 per year and a mortality between 3% and 40% depending on etiology, age, SE type and duration. Generalized convulsive forms of SE (GTCSE), in particular, require aggressive treatment. Presently, only 55–80% of cases of GTCSE are controlled by initial therapy. Therefore, there is a need for new options for the treatment of SE. Here we review the current standard treatment including recent advances and provide a summary of preclinical and clinical data regarding treatment options which may become available in the near future. The initial treatment of SE usually consists of a benzodiazepine (preferably lorazepam 0.1 mg/kg) followed by phenytoin or fosphenytoin or valproic acid (where approved for SE therapy). With intravenous formulations of levetiracetam, available since 2006, and lacosamide, which is expected for autumn of 2008, new treatment options have become available, that should be evaluated in prospective controlled trials. If SE remains refractory, the induction of general anaesthesia using propofol, midazolam, thiopental, or pentobarbital is warranted in GTCSE. PMID:21180563
Lampin, M-E; Dorkenoo, A; Lamblin, M-D; Botte, A; Leclerc, F; Auvin, S
Morbidity and mortality are high in children with refractory status epilepticus (RSE). Here, we assess the efficacy of midazolam for RSE in children. This was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008. The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failure. We recorded 29 patients with RSE during the study period: 26 were treated with midazolam, including two where midazolam replaced thiopenthal because of hypotension. Midazolam successfully controlled RSE in 58% of patients. Mean delay to cessation of RSE was 48+/-65 minutes. Hypotension was observed in 8% of midazolam-treated patients and 71% of thiopenthal-treated patients. Overall mortality was 15% (4/26). Two deaths occurred long after the cessation of RSE. None of the deaths occurred in midazolam-treated patients. Midazolam is an efficient treatment for RSE in children. Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE.
Salami, Pariya; Lévesque, Maxime; Avoli, Massimo
Status epilepticus (SE) is defined as a seizure lasting more than 5 min or a period of recurrent seizures without recovery between them. SE is a serious emergency condition that requires immediate intervention; therefore, identifying SE electrophysiological markers may translate in prompt care to stop it. Here, we analyzed the EEG signals recorded from the CA3 region of the hippocampus and the entorhinal cortex in rats that responded to systemic administration of 4-aminopyridine (4AP) by generating either isolated seizures or seizures progressing to SE. We found that high frequency oscillations (HFOs) – which can be categorized as ripples (80–200 Hz) and fast ripples (250–500 Hz) – had different patterns of occurrence in the two groups (n = 5 for each group). Specifically, fast ripples in CA3 and entorhinal cortex of the SE group occurred at higher rates than ripples, both during the ictal and post-ictal periods when compared to the HFOs recorded from the isolated seizure group. Our data reveal that different patterns of HFO occurrence can pinpoint seizures progressing to SE, thus suggesting the involvement of different neuronal networks at the termination of seizure discharges. PMID:27018321
Wulsin, Aynara C.; Herman, James P.; Danzer, Steve C.
Status epilepticus (SE) induces rapid hyper-activation of the hypothalamo–pituitary–adrenocortical (HPA) axis. HPA axis hyperactivity results in excess exposure to high levels of circulating glucocorticoids, which are associated with neurotoxicity and depression-like behavior. These observations have led to the hypothesis that HPA axis dysfunction may exacerbate SE-induced brain injury. To test this hypothesis, we used the mouse pilocarpine model of epilepsy to determine whether use of the glucocorticoid receptor antagonist RU486 can attenuate hippocampal pathology following SE. Excess glucocorticoid secretion was evident 1 day after SE in the mice, preceding the development of spontaneous seizures (which can take weeks to develop). RU486 treatment blocked the SE-associated elevation of glucocorticoid levels in pilocarpine-treated mice. RU486 treatment also mitigated the development of hippocampal pathologies induced by SE, reducing loss of hilar mossy cells and limiting pathological cell proliferation in the dentate hilus. Mossy cell loss and accumulation of ectopic hilar cells are positively correlated with epilepsy severity, suggesting that early treatment with glucocorticoid antagonists could have anti-epileptogenic effects. PMID:27965624
Florence, Kiruba; Manisha, Lalan; Kumar, Babbar Anil; Ankur, Kaul; Kumar, Mishra Anil; Ambikanandan, Misra
The aim of the present investigation was to prepare and characterize clobazam mucoadhesive microemulsion (CZMME) to assess brain drug uptake and protection against pentylenetetrazole (PTZ)-induced convulsions in mice. Clobazam microemulsion (CZME) and CZMME were prepared by titration method and characterized. Brain uptake and pharmacokinetic parameters were calculated from drug concentration in mice brain versus time plots following intranasal administration of radiolabeled CZME and CZMME, intravenous and intranasal administration of radiolabeled clobazam solution. Gamma scintigraphy imaging of rabbit brain following intranasal administration was performed. Formulations were investigated for the onset of seizures in PTZ-challenged mice. Brain targeting efficiency and direct nose-to-brain transport percentage for mucoadhesive microemulsion suggested an improved brain uptake following intranasal administration. The findings were supported by gamma scintigraphy images. Delay in onset of PTZ-induced seizures with CZMME compared with positive control and placebo-treated groups confirmed the improved brain uptake. However, extensive animal studies followed by clinical trials are necessary to develop a product suitable for emergencies of acute seizures in status epilepticus and patients suffering from drug tolerance and hepatic impairment on long-term use in treatment of epilepsy, schizophrenia, and anxiety.
Wilcox, Karen S.; Gee, James M.; Gibbons, Meredith B.; Tvrdik, Petr; White, John A.
Temporal lobe epilepsy (TLE) is a devastating seizure disorder that is often caused by status epilepticus (SE). Temporal lobe epilepsy can be very difficult to control with currently available antiseizure drugs, and there are currently no disease-modifying therapies that can prevent the development of TLE in those patients who are at risk. While the functional changes that occur in neurons following SE and leading up to TLE have been well studied, only recently has attention turned to the role in epileptogenesis of astrocytes, the other major cell type of the brain. Given that epilepsy is a neural circuit disorder, innovative ways to evaluate the contributions that both neurons and astrocytes make to aberrant circuit activity will be critical for the understanding of the emergent network properties that result in seizures. Recently described approaches using genetically encoded calcium-indicating proteins can be used to image dynamic calcium transients, a marker of activity in both neurons and glial cells. It is anticipated that this work will lead to novel insights into the process of epileptogenesis at the network level and may identify disease-modifying therapeutic targets that have been missed because of a largely neurocentric view of seizure generation following SE. PMID:26219575
Al-Busaidi, Mujahid; Burad, Jyoti; Al-Belushi, Asma; Gujjar, Arun
We present a case of a 38-year-old woman who was at eight weeks of gestation and was admitted to Sultan Qaboos University Hospital with refractory status epilepticus (SE). She presented with a two-day history of fever and a depressed level of consciousness that was followed with generalized tonic-clonic seizures. She progressed to refractory SE that required intubation and mechanical ventilation. Autoimmune workup was suggestive of Hashimoto’s encephalopathy (HE) as suggested by the high levels of thyroid antibodies. Her magnetic resonance imaging showed bilateral hippocampal and basal ganglia hyperintensities, and electroencephalogram showed bilateral frontal epileptiform discharges. Other autoimmune workup was negative. Intravenous anesthetics were started including propofol, midazolam, ketamine, and thiopentone. She was started on multiple immunosuppressive therapies. Multiple antiepileptics were used including phenytoin, lamotrigine, levetiracetam, sodium valproate, clobazam, phenobarbital, and lacosamide. The outcome was unusual in terms of refractoriness to immunotherapy treatment despite a confirmed diagnosis. We did a literature review of all cases with HE presenting with SE with their clinical characteristics and outcome. PMID:28584608
Swisher, Christa B; Doreswamy, Meghana; Husain, Aatif M
To determine the efficacy of pregabalin (PGB) in treatment of frequent nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE) in critically ill patients. In this retrospective study, 21 patients were identified as having received pregabalin for the treatment of NCS as determined by continuous electroencephalographic monitoring. The patients were considered to be responders if their seizures were terminated within 24h of initiation of PGB without the addition of another antiepileptic agent. Of the 21 patients who received PGB for treatment of NCS or NCSE, 11 (52%) were responders. PGB was administered via a nasogastric tube or orally and was the 2nd to 4th agent used. The average initial dose and total daily dose of PGB was similar in the responders and non-responders (342mg vs. 360mg, respectively). PGB was more effective in aborting NCS (9 patients, 82%) than NCSE (2 patients, 18%). Of the 9 brain tumor patients, PGB resulted in seizure cessation in 67% (6 patients). In contrast, all patients with hypoxic injury (4) did not respond to PGB. The responders were noted to have better clinical outcome (64% vs. 9% discharged home). Most of the patients tolerated the medication without any significant short term adverse effects, except two patients who were noted to have dizziness and sedation. Pregabalin may be safe option for add-on treatment for nonconvulsive seizures in critically ill patients when conventional therapy fails. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Niquet, Jerome; Baldwin, Roger; Norman, Keith; Suchomelova, Lucie; Lumley, Lucille; Wasterlain, Claude G
Early maladaptive internalization of synaptic GABAA receptors (GABAAR) and externalization of NMDA receptors (NMDAR) may explain the time-dependent loss of potency of standard anti-epileptic drugs (AED) in refractory status epilepticus (SE). We hypothesized that correcting the effects of changes in GABAAR and NMDAR would terminate SE, even when treatment is delayed 40 minutes. SE was induced in adult Sprague-Dawley rats with a high dose of lithium and pilocarpine. The GABAAR agonist midazolam, the NMDAR antagonist ketamine and the AED valproate were injected 40 min after SE onset in combination or as monotherapy. The midazolam-ketamine-valproate combination was more efficient than triple-dose midazolam, ketamine or valproate monotherapy or higher-dose dual therapy in reducing several parameters of SE severity. Triple therapy also reduced SE-induced acute neuronal injury and spatial memory deficits. In addition, simultaneous triple therapy was more efficient than sequential triple therapy: giving the three drugs simultaneously was more efficient at stopping seizures than the standard practice of giving them sequentially. Furthermore, midazolam-ketamine-valproate therapy suppressed seizures far better than the midazolam-fosphenytoin-valproate therapy, which follows evidence-based AES guidelines. These results show that a treatment aimed at correcting maladaptive GABAAR and NMDAR trafficking can reduce the severity of SE and its long-term consequences. Published by Elsevier Inc.
Verrotti, Alberto; Ambrosi, Michela; Pavone, Piero; Striano, Pasquale
Status Epilepticus (SE) is the most common neurological emergency of childhood. It requires prompt administration of appropriately selected anti-seizure medications. Areas covered: Following a distinction between estabilished and emergent drugs, we present pharmacological treatment options and their clinical utility in children, with a short mention on alternatives to drug treatment. We also propose an algorithm for the management of pediatric SE. For this review a Pubmed, Medline and Embase search was performed. Expert opinion: In early SE in children, in the prehospital setting, rectal diazepam or buccal midazolam are efficacious drugs; whereas in the hospital setting, intravenous lorazepam or diazepam are indicated. As regard estabilished stage of SE, in addition to the 'classic' compounds, such as phenytoin and phenobarbital, other drugs such as valproic acid, levetiracetam and lacosamide have been demonstrated efficacious. Treatment recommendations of refractory SE depend on retrospective case series and uncontrolled studies. We reported experiences about the use of midazolam, propofol, ketamine and lidocaine. They could be a valid option, but further prospective studies are necessary. Over the last few decades, important advances in basic mechanisms underlying refractory SE have been achieved, but few data are available regarding management of these stages.
Zhvania, Mzia G; Ksovreli, Mariam; Japaridze, Nadezhda J; Lordkipanidze, Tamar G
A pentylenetetrazol (PTZ)-induced status epilepticus model in rats was used in the study. The brains were studied one month after treatment. Ultrastructural observations using electron microscopy performed on the neurons, glial cells, and synapses, in the hippocampal CA1 region of epileptic brains, demonstrated the following major changes over normal control brain tissue. (i) There is ultrastructural alterations in some neurons, glial cells and synapses in the hippocampal CA1 region. (ii) The destruction of cellular organelles and peripheral, partial or even total chromatolysis in some pyramidal cells and in interneurons are observed. Several astrocytes are proliferated or activated. Presynaptic terminals with granular vesicles and degenerated presynaptic profiles are rarely observed. (iii) The alterations observed are found to be dependent on the frequency of seizure activities following the PTZ treatment. It was observed that if seizure episodes are frequent and severe, the ultrastructure of hippocampal area is significantly changed. Interestingly, the ultrastructure of CA1 area is found to be only moderately altered if seizure episodes following the status epilepticus are rare and more superficial; (iv) alterations in mitochondria and dendrites are among the most common ultrastructural changes seen, suggesting cell stress and changes to cellular metabolism. These morphological changes, observed in brain neurons in status epilepticus, are a reflection of epileptic pathophysiology. Further studies at the chemical and molecular level of neurotransmitter release, such as at the level of porosomes (secretory portals) at the presynaptic membrane, will further reveal molecular details of these changes. Copyright © 2015 Elsevier Ltd. All rights reserved.
Dilena, Robertino; Nebbia, Gabriella; Fiorica, Lorenzo; Farallo, Marcello; Degrassi, Irene; Gozzo, Francesca; Pelliccia, Veronica; Barbieri, Sergio; Cossu, Massimo; Tassi, Laura
Posterior reversible encephalopathy syndrome (PRES) with status epilepticus may occur after liver transplant. This may rarely lead to refractory epilepsy and hippocampal sclerosis (HS). We report the first case of epilepsy surgery in a liver-transplanted patient with refractory temporal lobe epilepsy. A 3-year-old girl underwent liver transplant for congenital biliary atresia. Four days after transplant she manifested PRES with status epilepticus, but she recovered within a couple of weeks. At the age of 5 years she started presenting complex partial seizures, that became refractory to antiepileptic drugs (AED), worsening psychosocial performances. The pre-surgical work-up identified a left HS and temporal pole alterations. A left antero-mesial temporal lobectomy was performed, leading to epilepsy remission and allowing AED withdrawal. Drug-resistant temporal lobe epilepsy and HS may occur as sequelae of PRES with status epilepticus related to liver transplant and cyclosporine use. In this setting early epilepsy surgery may reduce the time of chronic exposure to AED and severe illness due to repeated seizures. This option might have additional advantages in the subgroup of epileptic patients with liver transplant, preserving the liver from the potential damage due to multiple AED trials and their interaction with commonly used immunosuppressant drugs. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Trinka, Eugen; Cock, Hannah; Hesdorffer, Dale; Rossetti, Andrea O; Scheffer, Ingrid E; Shinnar, Shlomo; Shorvon, Simon; Lowenstein, Daniel H
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
Wu, Mengqian; Hao, Nanya; Yan, Bo; Chi, Xiaosa; Zhou, Dong
Valproate is an effective wide-spectrum anti-epileptic drug that is also known to be teratogenic. Its administration in epileptic women remains controversial. This report aims to draw more attention to valproate adjustment before and during pregnancy. We collected medical records of pregnant women with epilepsy at West China Hospital in Chengdu, China who developed status epilepticus during pregnancy after valproate withdrawal or reduction in dose from January 2013 to July 2015. A total of 281 pregnancies in patients with epilepsy were examined; 6 episodes of status epilepticus occurred during these pregnancies. Four patients with status epilepticus took long-term valproate before pregnancy. Among them, 2 patients stopped taking valproate 3 months prior to pregnancy, and 2 patients discontinued valproate or reduced their valproate dose when pregnancy was confirmed. All 4 suffered from a convulsive status epilepticus; 3 experienced an increased frequency of seizures. One child was diagnosed with neonatal asphyxia, hypoxic-ischemic encephalopathy, and neonatal pneumonia. Valproate adjustment prior to or during pregnancy may result in deterioration of seizure control, which may include resultant status epilepticus. Valproate during pregnancy increases the risk of major congenital malformations, but the significance of maintaining seizure control in pregnant women should be also taken into consideration. Open and careful discussion with every pregnant woman with epilepsy should discuss the risk-benefit ratio of epilepsy medications. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Blades Golubovic, Susan; Rossmeisl, John H
To review current knowledge of the etiopathogenesis, diagnosis, and consequences of status epilepticus (SE) in veterinary patients. Human and veterinary literature, including clinical and laboratory research and reviews. Status epilepticus is a common emergency in dogs and cats, and may be the first manifestation of a seizure disorder. It results from the failure of termination of an isolated seizure. Multiple factors are involved in SE, including initiation and maintenance of neuronal excitability, neuronal network synchronization, and brain microenvironmental contributions to ictogenesis. Underlying etiologies of epilepsy and SE in dogs and cats are generally classified as genetic (idiopathic), structural-metabolic, or unknown. Diagnosis of convulsive SE is usually made based on historical information and the nature of the seizures. Patient specific variables, such as the history, age of seizure onset, and physical and interictal neurological examination findings can help hone the rule out list, and are used to guide selection and prioritization of diagnostic tests. Electroencephalographic monitoring is routinely used in people to diagnose SE and guide patient care decisions, but is infrequently performed in veterinary medicine. Nonconvulsive status epilepticus has been recognized in veterinary patients; routine electroencephalography would aid in the diagnosis of this phenomenon in dogs and cats. Status epilepticus is a medical emergency that can result in life-threatening complications involving the brain and systemic organs. Status epilepticus often requires comprehensive diagnostic testing, treatment with multiple anticonvulsant agents, and intensive supportive care. © Veterinary Emergency and Critical Care Society 2017.
Elting, Jan Willem; Naalt, Joukje van der; Fock, Johanna Maria
Hypothermia can reduce seizure frequency in animal models of status epilepticus, and its effectiveness in human status epilepticus has been reported occasionally. We report an infant with hemimegalencephaly who presented with generalized status epilepticus. After high dose intravenous drug therapy, this converted to focal status epilepticus in the right occipital region. A sudden cessation of all seizure activity was found to coincide with accidental hypothermia. After application of mild continuous hypothermia, a marked reduction of seizure frequency occurred, which allowed reduction of intravenous drug doses and discharge from the IC unit. Ultimately, hemispherectomy was needed to achieve long term seizure control. The therapeutic effect of hypothermia should be further investigated in patients with refractory status epilepticus. When used in combination with anti-epileptic drugs, seizure control may be achieved at lower doses. Hypothermia may obviate the need for potentially dangerous barbiturate therapy. This case demonstrates that even a mild degree of hypothermia (+/-36 degrees C) can be remarkably effective. Copyright (c) 2009. Published by Elsevier Ltd.
Chen, Xiao-Qiao; Zhang, Wei-Na; Yang, Zhi-Xian; Zhao, Meng; Cai, Fang-Cheng; Huang, Shao-Ping; Gao, Li; Pang, Bao-Dong; Chen, Xi; Zou, Li-Ping
Electrical status epilepticus during sleep is characterized by epilepsy, a specific electroencephalographic pattern, and neuropsychological impairment. This study aims to evaluate the efficacy and safety of levetiracetam in treating children with electrical status epilepticus during sleep. A multicenter, retrospective, open-label study enrolled 73 children (mean age: 8 years) affected by electrical status epilepticus during sleep. The efficacy was rated according to the seizure frequency and electroencephalography response. After a mean treatment period of 19 months (range: 6 to 24 months), 33 (63.5%) of 52 patients became seizure-free or had experienced remarkable reduction in seizures. The electrical status epilepticus of 41 (56.2%) of 73 patients disappeared off their electroencephalography. The electroencephalography efficacy of levetiracetam treatment was noted in the monotherapy (61.9%) and add-on (53.9%) groups. The clinical (67.7%) and electroencephalography (64.3%) response rates of the idiopathic group were better than those of the symptomatic group (57.1% and 45.2%, respectively). No patient discontinued the trial because of intolerability of side effects. Levetiracetam is effective in individuals with electrical status epilepticus during sleep with tolerable side effects. Copyright © 2014 Elsevier Inc. All rights reserved.
Aftab, Awais; VanDercar, Ashley; Alkhachroum, Ayham; LaGrotta, Christine; Gao, Keming
The clinical presentation and risk factors of nonconvulsive status epilepticus (NCSE) in the context of electroconvulsive therapy (ECT) are poorly understood, and guidance regarding diagnosis and management remains scarce. In this article, we identify case reports of ECT-induced NCSE from literature, and discuss the presentation, diagnosis, and management of these cases in the context of what is known about NCSE from the neurology literature. A literature search on PubMed for case reports of NCSE after ECT. We identified 13 cases for this review. Diagnosis in all cases was based on clinical features and electroencephalogram (EEG) findings. Clinical presentation was altered mental status or unresponsiveness, with subtle motor phenomena in some cases. All cases had nonspecific risk factors that have been associated with prolonged seizures and convulsions, such as recent discontinuation/reduction of benzodiazepines or anticonvulsants, and concurrent use of antipsychotics and antidepressants. All patients were treated with either benzodiazepines or antiepileptic agents. Outcomes in these post-ECT NCSE cases were generally favorable. Although rare, post-ECT NCSE should be kept in mind by physicians when confusion or unresponsiveness develops and continues after ECT; multilead EEG is gold standard for diagnosis. An intravenous (IV) antiepileptic drug (AED) challenge can help clarify the diagnosis. Initial treatment is recommended with IV benzodiazepines, with a repeat dose if necessary. If seizures persist, IV AEDs are warranted. NCSE refractory to this treatment should be treated with a scheduled IV or oral AED. Serial multilead EEGs should be used to monitor resolution of symptoms. NCSE after ECT is a rare but recognizable clinical event. A high clinical suspicion and low threshold for EEG is necessary for prompt diagnosis. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.
Abend, Nicholas S.; Wagenman, Katherine L.; Blake, Taylor P.; Schultheis, Maria T.; Radcliffe, Jerilynn; Berg, Robert A.; Topjian, Alexis A.; Dlugos, Dennis J.
Purpose Electrographic seizures (ES) and electrographic status epilepticus (ESE) are common in children in the pediatric intensive care unit (PICU) with acute neurologic conditions, and ESE is associated with worse functional and quality of life outcomes. As an exploratory study, we aimed to determine if ESE was associated with worse outcomes using more detailed neurobehavioral measures. Methods Three hundred children with an acute neurologic condition and altered mental status underwent clinically indicated EEG monitoring and were enrolled in a prospective observational study. We obtained follow-up data from subjects who were neurodevelopmentally normal prior to PICU admission. We evaluated for associations between ESE and adaptive behavior (Adaptive Behavior Assessment System-II, ABAS-II), behavioral and emotional problems (Child Behavior Checklist, CBCL), and executive function (Behavior Rating Inventory of Executive Function, BRIEF) using linear regression analyses. A p-value of <0.05 was considered significant. Results 137 of 300 subjects were neurodevelopmentally normal prior to PICU admission. We obtained follow-up data from 36 subjects for CBCL, 32 subjects for ABAS, and 20 subjects for BRIEF. The median duration from admission to follow-up was 2.6 years (IQR 1.2–3.8). There were no differences in the acute care variables (age, sex, mental status category, intubation status, paralysis status, acute neurologic diagnosis category, seizure category, EEG background category, or short-term outcome) between subjects with and without follow-up data for any of the outcome measures. On univariate analysis, significant differences were not identified for CBCL total problem (ES coefficient −4.1, p=0.48; ESE coefficient 8.9, p=0.13) or BRIEF global executive function scores (ES coefficient 2.1, p=0.78; ESE coefficient 14.1, p=0.06), although there were trends towards worse scores in subjects with ESE. On univariate analysis, ES was not associated with worse scores
Liu, Jinzhi; Li, Xiaolin; Chen, Liguang; Xue, Ping; Yang, Qianqian; Wang, Aihua
Calcineurin plays an important role in the development of neuronal excitability, modulation of receptor's function and induction of apoptosis in neurons. It has been established in kindling models that status epilepticus induces brain focal edema and astrocyte activation. However, the role of calcineurin in brain focal edema and astrocyte activation in status epilepticus has not been fully understood. In this study, we employed a model of lithium-pilocarpine-induced status epilepticus and detected calcineurin expression in hippocampus by immunoblotting, brain focal edema by non-invasive magnetic resonance imaging (MRI-7T) and astrocyte expression by immunohistochemistry. We found that the brain focal edema was seen at 24 h after status epilepticus, and astrocyte expression was obviously seen at 7 d after status epilepticus. Meanwhile, calcineurin expression was seen at24 h and retained to 7 d after status epilepticus. A FK506, a calcineurin inhibitor, remarkably suppressed the status epilepticus-induced brain focal edema and astrocyte expression. Our data suggested that calcineurin overexpression plays a very important role in brain focal edema and astrocyte expression. Therefore, calcineurin may be a novel candidate for brain focal edema occurring and intracellular trigger of astrogliosis in status epilepticus.
Hafeez, Baria; Paolicchi, Juliann; Pon, Steven; Howell, Joy D; Grinspan, Zachary M
Status epilepticus is a common neurologic emergency in children. Pediatric medical centers often develop protocols to standardize care. Widespread adoption of electronic health records by hospitals affords the opportunity for clinicians to rapidly, and electronically evaluate protocol adherence. We reviewed the clinical data of a small sample of 7 children with status epilepticus, in order to (1) qualitatively determine the feasibility of automated data extraction and (2) demonstrate a timeline-style visualization of each patient's first 24 hours of care. Qualitatively, our observations indicate that most clinical data are well labeled in structured fields within the electronic health record, though some important information, particularly electroencephalography (EEG) data, may require manual abstraction. We conclude that a visualization that clarifies a patient's clinical course can be automatically created using the patient's electronic clinical data, supplemented with some manually abstracted data. Future work could use this timeline to evaluate adherence to status epilepticus clinical protocols. © The Author(s) 2015.
Rison, Richard A; Ko, David Y
Propofol is a widely used rapidly acting sedating or hypnotic agent in the intensive care setting. It is generally considered safe in both pediatric and adult patients and has been used frequently in cases of refractory status epilepticus. The formulation of propofol is highly lipophilic to facilitate central nervous system penetration and has a high fat content, and prolonged infusions have been known to cause both extrahepatic complications and hepatomegaly secondary to fatty liver. Whereas extrahepatic manifestations of prolonged propofol infusions have been well reported in non-neurologic intensive care patients, cases of pathologically confirmed fatty liver in patients with status epilepticus are relatively few. Furthermore, these cases of hepatomegaly and fatty liver have been also in the context of concomitant extrahepatic side effects. We report on a pediatric patient with refractory status epilepticus treated with a prolonged propofol infusion who developed isolated pathologically confirmed fatty liver without the usually reported extrahepatic manifestations.
Zeiler, F. A.
Refractory status epilepticus (RSE) and superrefractory status epilepticus (SRSE) pose a difficult clinical challenge. Multiple cerebral receptor and transporter changes occur with prolonged status epilepticus leading to pharmacoresistance patterns unfavorable for conventional antiepileptics. In particular, n-methyl-d-aspartate (NMDA) receptor upregulation leads to glutamate mediated excitotoxicity. Targeting these NMDA receptors may provide a novel approach to otherwise refractory seizures. Ketamine has been utilized in RSE. Recent systematic review indicates 56.5% and 63.5% cessation in seizures in adults and pediatrics, respectively. No complications were described. We should consider earlier implementation of ketamine or other NMDA receptor antagonists, for RSE. Prospective study of early implementation of ketamine should shed light on the role of such medications in RSE. PMID:25649724
Oderiz, Carolina Cuello; Aberastury, Marina; Besocke, Ana Gabriela; Sinner, Jorge; Comas-Guerrero, Betiana; Ciraolo, Carlos Alberto; Pasteris, Maria Concepción; Silva, Walter Horacio; García, María Del Carmen
Neurosurgery appears to be a reasonable alternative in carefully selected patients with refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE). We discuss the optimal timing of the surgery and the use of previous stereoelectroencephalography (SEEG) invasive evaluation. We identified 3 patients (two pediatric and one adult) who underwent epilepsy surgery because of RSE or SRSE from our epilepsy surgery database, one of them with previous SEEG. Status epilepticus resolved acutely in all of them with no mortality and no substantial morbidity. At follow-up (median: 2 years), 1 patient was seizure-free, and 2 had significant improvement. Surgery should be considered in all cases of RSE and SRSE early in the course of the evolution of the disease.
Marsch, Stephan; Fuhr, Peter; Kaplan, Peter W.; Rüegg, Stephan
Objective: To evaluate the risks of continuously administered IV anesthetic drugs (IVADs) on the outcome of adult patients with status epilepticus (SE). Methods: All intensive care unit patients with SE from 2005 to 2011 at a tertiary academic medical care center were included. Relative risks were calculated for the primary outcome measures of seizure control, Glasgow Outcome Scale score at discharge, and death. Poisson regression models were used to control for possible confounders and to assess effect modification. Results: Of 171 patients, 37% were treated with IVADs. Mortality was 18%. Patients with anesthetic drugs had more infections during SE (43% vs 11%; p < 0.0001) and a 2.9-fold relative risk for death (2.88; 95% confidence interval 1.45–5.73), independent of possible confounders (i.e., duration and severity of SE, nonanesthetic third-line antiepileptic drugs, and critical medical conditions) and without significant effect modification by different grades of SE severity and etiologies. As IVADs were used after first- and second-line drugs failed, there was a correlation between treatment-refractory SE and the use of IVADs, leading to insignificant results regarding the risk of IVADs and outcome after additional adjustment for refractory SE. Conclusion: Our findings heighten awareness regarding adverse effects of IVADs. Randomized controlled trials are needed to further clarify the association of IVADs with outcome in patients with SE. Classification of evidence: This study provides Class III evidence that patients with SE receiving IVADs have a higher proportion of infection and an increased risk of death as compared to patients not receiving IVADs. PMID:24319039
Zaccara, Gaetano; Giannasi, Gianfranco; Oggioni, Roberto; Rosati, Eleonora; Tramacere, Luciana; Palumbo, Pasquale
Convulsive status epilepticus (CSE) is a medical emergency associated with high mortality and morbidity. The most recent definition of CSE is a convulsive seizure lasting more than 5min or consecutive seizures without recovery of consciousness. In adults, for the treatment of the early stages of CSE, diazepam, lorazepam or midazolam are the most common treatments, although the choice of agent seems less important than rapid treatment. Midazolam, when administered intramuscularly (best evidence), buccally, or nasally, is effective and safe in the pre-hospital setting. The antiepileptic drugs, phenytoin, valproate, levetiracetam and, more recently lacosamide, are used in CSE that persists after first-line treatments (established CSE). Phenytoin is more difficult to administer and is less well tolerated. Evidence of the efficacy of lacosamide is scarce. Anaesthetics are the drugs of choice for the treatment of refractory CSE (not responding to second-line drugs). Midazolam seems to be the best tolerated and is the most often used drug, followed by propofol and thiopental (pentobarbital in the USA). A few studies indicate that ketamine is effective with the possible advantage that it can be co-administered with other anaesthetics, such as midazolam or propofol. CSE becomes super-refractory after more than 24h of appropriate treatments and may last weeks. Several anaesthetics have been proposed but evidence is scarce. Autoimmune refractory CSE has been recently identified, and early treatment with immuno-modulatory agents (corticosteroids and IV immunoglobulins and also second-line agents such as cyclophosphamide and rituximab followed by chronic immunosuppressive treatment) is now recommended by many experts. Copyright © 2017. Published by Elsevier Ltd.
Goodkin, Howard P.; Joshi, Suchitra; Mtchedlishvili, Zakaria; Brar, Jasmit; Kapur, Jaideep
It is proposed that a reduced surface expression of GABAA receptors (GABARs) contributes to the pathogenesis of status epilepticus (SE), a condition characterized by prolonged seizures. This hypothesis was based on the finding that prolonged epileptiform bursting (repetitive bursts of prolonged depolarizations with superimposed action potentials) in cultures of dissociated hippocampal pyramidal neurons (dissociated cultures) results in the increased intracellular accumulation of GABARs. However, it is not known whether this rapid modification in the surface-expressed GABAR pool results from selective, subunit-dependent or nonselective, subunit-independent internalization of GABARs. In hippocampal slices obtained from animals undergoing prolonged SE (SE-treated slices), we found that the surface expression of the GABARβ2/3 and γ2 subunits was reduced, whereas that of the δ subunit was not. Complementary electrophysiological recordings from dentate granule cells in SE-treated slices demonstrated a reduction in GABAR-mediated synaptic inhibition, but not tonic inhibition. A reduction in the surface expression of the γ2 subunit, but not the δ subunit was also observed in dissociated cultures and organotypic hippocampal slice cultures when incubated in an elevated KCl external medium or an elevated KCl external medium supplemented with NMDA, respectively. Additional studies demonstrated that the reduction in the surface expression of the γ2 subunit was independent of direct ligand binding of the GABAR. These findings demonstrate that the regulation of surface-expressed GABAR pool during SE is subunit-specific and occurs independent of ligand binding. The differential modulation of the surface expression of GABARs during SE has potential implications for the treatment of this neurological emergency. PMID:18322097
Spatola, Marianna; Novy, Jan; Du Pasquier, Renaud; Dalmau, Josep; Rossetti, Andrea O
Inflammation-related epilepsy is increasingly recognized; however, studies on status epilepticus (SE) are very infrequent. We therefore aimed to determine the frequency of inflammatory etiologies in adult SE, and to assess related demographic features and outcomes. This was a retrospective analysis of a prospective registry of adult patients with SE treated in our center, from January 2008 to June 2014, excluding postanoxic causes. We classified SE episodes into 3 etiologic categories: infectious, autoimmune, and noninflammatory. Demographic and clinical variables were analyzed regarding their relationship to etiologies and functional outcome. Among the 570 SE consecutive episodes, 33 (6%) were inflammatory (2.5% autoimmune; 3.3% infectious), without any change in frequency over the study period. Inflammatory SE episodes involved younger patients (mean age 53 vs 61 years, p = 0.015) and were more often refractory to initial antiepileptic treatment (58% vs 38%, odds ratio = 2.19, 95% confidence interval = 1.07-4.47, p = 0.041), despite similar clinical outcome. Subgroup analysis showed that, compared with infectious SE episodes, autoimmune SE involved younger adults (mean age 44 vs 60 years, p = 0.017) and was associated with lower morbidity (return to baseline conditions in 71% vs 32%, odds ratio = 5.41, 95% confidence interval = 1.19-24.52, p = 0.043) without any difference in mortality. Despite increasing awareness, inflammatory SE etiologies were relatively rare; their occurrence in younger individuals and higher refractoriness to treatment did not have any effect on outcome. Autoimmune SE episodes also occurred in younger patients, but tended to have better outcomes in survivors than infectious SE. © 2015 American Academy of Neurology.
Niquet, Jerome; Gezalian, Michael; Baldwin, Roger; Wasterlain, Claude G
Pharmacoresistance develops quickly during repetitive seizures, and refractory status epilepticus (RSE) remains a therapeutic challenge. The outcome of RSE is poor, with high mortality and morbidity. New treatments are needed. Deep hypothermia (20°C) is used clinically during reconstructive cardiac surgery and neurosurgery, and has proved safe and effective in those indications. We tested the hypothesis that deep hypothermia reduces RSE and its long-term consequences. We used a model of SE induced by lithium and pilocarpine and refractory to midazolam. Several EEG measures were recorded in both hypothermic (n = 17) and normothermic (n = 20) animals. Neuronal injury (by Fluoro-Jade B), cell-mediated inflammation, and breakdown of the blood-brain barrier (BBB) (by immunohistochemistry) were studied 48 h following SE onset. Normothermic rats in RSE seized for 4.1 ± 1.1 h, and at 48 h they displayed extensive neuronal injury in many brain regions, including hippocampus, dentate gyrus, amygdala, entorhinal and pyriform cortices, thalamus, caudate/putamen, and the frontoparietal neocortex. Deep hypothermia (20°C) of 30 min duration terminated RSE within 12 min of initiation of hypothermia, reduced EEG power and seizure activity upon rewarming, and eliminated SE-induced neuronal injury in most animals. Normothermic rats showed widespread breakdown of the BBB, and extensive macrophage infiltration in areas of neuronal injury, which were completely absent in animals treated with hypothermia. These results suggest that deep hypothermia may open a new therapeutic avenue for the treatment of RSE and for the prevention of its long-term consequences.
Madžar, Dominik; Geyer, Anna; Knappe, Ruben U; Gollwitzer, Stephanie; Kuramatsu, Joji B; Gerner, Stefan T; Hamer, Hajo M; Huttner, Hagen B
Clobazam (CLB) is a well characterized antiepileptic drug (AED) that differs from other benzodiazepines by its basic chemical structure and pharmacodynamic properties. Only one previous study examined the efficacy of CLB as add-on therapy in refractory status epilepticus (RSE). We analyzed RSE episodes treated in our institution between 2001 and 2012. Successful treatment with CLB was scored if CLB was the last AED added to therapy before RSE termination. We assessed the differences between patients with and without CLB and correlated CLB with outcome. Among patients treated with CLB, we studied responders and non-responders and compared our CLB cohort with recently published data. CLB was part of the AED regimen in 24/70 (34.3 %) RSE episodes. In six of these (25.0 %) RSE resolution was attributed to CLB. Baseline characteristics of episodes with and without CLB treatment showed no significant differences and RSE termination rates were very similar (83.3 % vs. 80.4 %). CLB was administered in clinically more complex RSE with longer RSE duration and worse outcome, but CLB was not related independently to outcome. Comparison of our results with previously published data revealed that baseline characteristics as well as CLB maintenance doses and time of treatment initiation were similar in both cohorts. CLB was less frequently the last AED added to RSE therapy in our patients indicating a lower treatment success rate than previously reported. CLB represents a reasonable AED and promising add-on agent for treatment of RSE. However, rates of successful CLB response were substantially lower than in a recently published study. Differing RSE characteristics and treatment strategies may account for the discrepancy between study results, as RSE etiologies and seizures types associated with unfavorable prognosis were more common in our cohort, while anesthetics tended to be less frequently applied to achieve seizure control.
Bleck, T P
Status epilepticus (SE) treatment should proceed on four fronts: termination of SE, prevention of recurrence, management of potential precipitating causes, and management of SE complications and underlying conditions. The intensity of the treatment should reflect the risk to the patient from SE, and drugs likely to depress respiration and blood pressure should initially be avoided. The Veterans Administration cooperative trial showed that when treating overt SE, first-line treatment success rates were: lorazepam 64.9%; phenobarbital 58.2%; diazepam/phenytoin 55.8%; and phenytoin alone 43.6%. The aggregate response rate to second-line agents for patients who did not respond to first-line agents was 7.0%, and it was 2.3% for third-line agents, raising the question of the efficacy of a second and third drug. The recommended treatment for generalized convulsive SE is to begin with lorazepam. As a second-line agent, phenytoin or fosphenytoin, is still recommended if SE control is not achieved within 5 to 7 min. Fosphenytoin achieves a free phenytoin level of about 2 micro/mL in 15 min, as opposed to 25 min with phenytoin itself. Moreover, fosphenytoin is safer and, despite higher cost, it may be cost-effective. High-dose barbiturates, high-dose benzodiazepines, and propofol are employed for major treatment for refractory SE. Patients at this stage should undergo continuous electroencephalogram monitoring. Once SE is controlled, prevention of seizure recurrence should be individualized to each patient. The major complications of generalized convulsive SE (GCSE), rhabdomyolysis and hyperthermia, should be watched for and treated.
Marcuse, Lara V; Lancman, Guido; Demopoulos, Alexis; Fields, Madeline
The prevalence of nonconvulsive status epilepticus (NCSE) in brain tumor patients is unknown. Since NCSE has been associated with significant mortality and morbidity, early identification is essential. This study describes the clinical and EEG characteristics, treatment, and outcome in brain tumor patients with NCSE. All patients admitted to Mount Sinai Hospital from 2009 to 2012 with an ICD-9 brain tumor code were cross-referenced with the epilepsy department's database. EEGs from matching patients were reviewed for NCSE. Relevant information from the medical records of the patients with NCSE was extracted. 1101 brain tumor patients were identified, of which 259 (24%) had an EEG and 24 (2%) had NCSE. The vast majority of seizures captured were subclinical with 13 patients (54%) having only subclinical seizures. Treatment resolved the NCSE in 22 patients (92%) with accompanying clinical improvement in 18 (75%) of those patients. Tumor recurrence or progression on MRI was associated with decreased 2-month survival (75% mortality, p=0.035) compared to stable tumors (20% mortality). Patients with metastatic disease had median survival from tumor diagnosis of 1.2 months. NCSE in brain tumor patients may be under diagnosed due to the frequent lack of outward manifestations and highly treatable with improvement in the majority of patients. NCSE patients with progressing brain lesions, tumor recurrence, or metastatic disease are at serious risk of mortality within 2 months. Continuous EEG monitoring in brain tumor patients with recent clinical seizures and/or a depressed level of consciousness may be critical in providing appropriate care. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Caraballo, Roberto Horacio; Flesler, Santiago; Armeno, Marisa; Fortini, Sebastian; Agustinho, Ariela; Mestre, Graciela; Cresta, Araceli; Buompadre, María Celeste; Escobal, Nidia
The ketogenic diet (KD) has been used as an alternative treatment for patients with refractory status epilepticus (SE). In this retrospective study we assess the efficacy and tolerability of the KD in patients with refractory SE. Between March 1, 2010 and January 1, 2014, 10 patients who met the diagnostic criteria of refractory SE seen at our department were placed on the KD and followed for a minimum of 6 months. Ketonuria was reached within 2-4 days (mean 3 days) for all patients. Seizures stopped in two patients and five patients had a 50-75% seizure reduction within 2-5 days (mean 2.5 days) following the onset of ketonuria and within 5-7 days (mean 5 days) following the onset of the diet. Three patients had a <50% seizure reduction and all of them had severe adverse events so the diet was discontinued. Seven patients remained on the diet for 6 months to 3 years (mean 1.5 years). In all seven patients within 4 months the seizures recurred, but their quality of life did not worsen. The frequency of the seizures consisted of weekly seizures in two, monthly seizures in two, occasional seizures in two, and isolated seizures in one. All of them kept a good tolerability of the diet. The KD is an effective and well-tolerated treatment option for patients with refractory SE. In patients with focal SE secondary to inflammatory or probably inflammatory diseases, the KD should be considered earlier in the course of the treatment. Copyright © 2014 Elsevier B.V. All rights reserved.
Lin, Jainn-Jim; Lin, Kuang-Lin; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong
A ketogenic diet has been used successfully to treat intractable epilepsy. However, the role of early intravenous initiation of ketogenic diet in the acute phase of super-refractory status epilepticus is not well-described. An intravenous ketogenic diet was administered to a boy with super-refractory status epilepticus. At 24 hours after intravenous ketogenic diet, moderate ketosis appeared, and thiamylal was successfully weaned at 70 hours after admission. An intravenous ketogenic regimen led to subsequent ketosis and seizure control in a child with super-refractory status epilepticus. Early induction of ketosis may be a novel strategy to effectively treat super-refractory status epilepticus. Although there are few data regarding the early use of intravenous ketogenic diet in the treatment of super-refractory status epilepticus, it may be considered an alternative option. Copyright © 2015 Elsevier Inc. All rights reserved.
Hayakawa, Itaru; Miyama, Sahoko; Inoue, Nobuaki; Sakakibara, Hiroshi; Hataya, Hiroshi; Terakawa, Toshiro
Pediatric convulsive status epilepticus with fever is common in the emergency setting but leads to severe neurological sequelae in some patients. To explore the epidemiology of convulsive status epilepticus with fever, a retrospective cohort covering all convulsive status epilepticus cases with fever seen in the emergency department of a tertiary care children's hospital were consecutively collected. Of the 381 consecutive cases gathered, 81.6% were due to prolonged febrile seizure, 6.6% to encephalopathy/encephalitis, 0.8% to meningitis, and 7.6% to epilepsy. In addition, seizures were significantly longer in encephalopathy/encephalitis cases than in prolonged febrile seizure cases (log rank test, P < .001). These results provide for the first time the pretest probability of final diagnoses in children with convulsive status epilepticus with fever in the emergency setting, and will help optimize the management of pediatric patients presenting to the emergency department with convulsive status epilepticus with fever. © The Author(s) 2016.
Meletti, Stefano; Giovannini, Giada; d’Orsi, Giuseppe; Toran, Lisa; Monti, Giulia; Guha, Rahul; Kiryttopoulos, Andreas; Pascarella, Maria Grazia; Martino, Tommaso; Alexopoulos, Haris; Spilioti, Martha; Slonkova, Jana
New-onset refractory status epilepticus (NORSE) is a rare but challenging condition occurring in a previously healthy patient, often with no identifiable cause. We describe the electro-clinical features and outcomes in a group of patients with NORSE who all demonstrated a typical magnetic resonance imaging (MRI) sign characterized by bilateral lesions of the claustrum. The group includes 31 patients (12 personal and 19 previously published cases; 17 females; mean age of 25 years). Fever preceded status epilepticus (SE) in 28 patients, by a mean of 6 days. SE was refractory/super-refractory in 74% of the patients, requiring third-line agents and a median of 15 days staying in an intensive care unit. Focal motor and tonic–clonic seizures were observed in 90%, complex partial seizures in 14%, and myoclonic seizures in 14% of the cases. All patients showed T2/FLAIR hyperintense foci in bilateral claustrum, appearing on average 10 days after SE onset. Other limbic (hippocampus, insular) alterations were present in 53% of patients. Within the personal cases, extensive search for known autoantibodies was inconclusive, though 7 of 11 patients had cerebrospinal fluid lymphocytic pleocytosis and 3 cases had oligoclonal bands. Two subjects died during the acute phase, one in the chronic phase (probable sudden unexplained death in epilepsy), and one developed a persistent vegetative state. Among survivors, 80% developed drug-resistant epilepsy. Febrile illness-related SE associated with bilateral claustrum hyperintensity on MRI represents a condition with defined clinical features and a presumed but unidentified autoimmune etiology. A better characterization of de novo SE is mandatory for the search of specific etiologies. PMID:28396650
Chamberlain, James M; Okada, Pamela; Holsti, Maija; Mahajan, Prashant; Brown, Kathleen M; Vance, Cheryl; Gonzalez, Victor; Lichenstein, Richard; Stanley, Rachel; Brousseau, David C; Grubenhoff, Joseph; Zemek, Roger; Johnson, David W; Clemons, Traci E; Baren, Jill
Benzodiazepines are considered first-line therapy for pediatric status epilepticus. Some studies suggest that lorazepam may be more effective or safer than diazepam, but lorazepam is not Food and Drug Administration approved for this indication. To test the hypothesis that lorazepam has better efficacy and safety than diazepam for treating pediatric status epilepticus. This double-blind, randomized clinical trial was conducted from March 1, 2008, to March 14, 2012. Patients aged 3 months to younger than 18 years with convulsive status epilepticus presenting to 1 of 11 US academic pediatric emergency departments were eligible. There were 273 patients; 140 randomized to diazepam and 133 to lorazepam. Patients received either 0.2 mg/kg of diazepam or 0.1 mg/kg of lorazepam intravenously, with half this dose repeated at 5 minutes if necessary. If status epilepticus continued at 12 minutes, fosphenytoin was administered. The primary efficacy outcome was cessation of status epilepticus by 10 minutes without recurrence within 30 minutes. The primary safety outcome was the performance of assisted ventilation. Secondary outcomes included rates of seizure recurrence and sedation and times to cessation of status epilepticus and return to baseline mental status. Outcomes were measured 4 hours after study medication administration. Cessation of status epilepticus for 10 minutes without recurrence within 30 minutes occurred in 101 of 140 (72.1%) in the diazepam group and 97 of 133 (72.9%) in the lorazepam group, with an absolute efficacy difference of 0.8% (95% CI, -11.4% to 9.8%). Twenty-six patients in each group required assisted ventilation (16.0% given diazepam and 17.6% given lorazepam; absolute risk difference, 1.6%; 95% CI, -9.9% to 6.8%). There were no statistically significant differences in secondary outcomes except that lorazepam patients were more likely to be sedated (66.9% vs 50%, respectively; absolute risk difference, 16.9%; 95% CI, 6.1% to 27.7%). Among
Lin, Jainn-Jim; Chou, Cheng-Che; Lan, Shih-Yun; Hsiao, Hsiang-Ju; Wang, Yu; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong; Lin, Kuang-Lin
Evidence for the beneficial effect of therapeutic burst-suppression coma in pediatric patients with febrile refractory status epilepticus is limited, and the clinical outcomes of this treatment strategy are largely unknown. Therefore, the aim of this study was to explore the outcomes of therapeutic burst-suppression coma in a series of children with febrile refractory status epilepticus. We retrospectively reviewed consecutive pediatric patients with febrile refractory status epilepticus admitted to our pediatric intensive care unit between January 2000 and December 2013. The clinical characteristics were analyzed. Thirty-five patients (23 boys; age range: 1-18years) were enrolled, of whom 28 (80%) developed super-refractory status epilepticus. All of the patients received the continuous administration of intravenous antiepileptic drugs for febrile refractory status epilepticus, and 26 (74.3%) achieved therapeutic burst-suppression coma. All of the patients received mechanical ventilatory support, and 26 (74.3%) received inotropic agents. Eight (22.9%) patients died within 1month. The neurologically functional outcomes at 6months were good in six (27.3%) of the 22 survivors, of whom two returned to clinical baseline. The patients with therapeutic burst-suppression coma were significantly associated with hemodynamic support than the patients with electrographic seizures control (p=0.03), and had a trend of higher 1-month mortality rate, worse 6months outcomes, and a longer duration of hospitalization. Our results suggest that therapeutic burst-suppression coma to treat febrile refractory status epilepticus may lead to an increased risk of hemodynamic instability and a trend of worse outcomes. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Hansen, Gregory; Joffe, Ari R; Bowman, Stephen M; Richer, Lawrence
It remains uncertain whether nonconvulsive seizures and nonconvulsive status epilepticus in pediatric traumatic brain injury are deleterious to the brain and/or impact the recovery from injury. Consequently, optimal electroencephalographic surveillance and management is unknown. We aimed to determine specialists' opinion regarding the detection and treatment of nonconvulsive seizures or nonconvulsive status epilepticus in pediatric traumatic brain injury, regardless of their practice. In 2012, 183 surveys were sent to all 93 neurologists, 27 neurosurgeons, and 63 intensivists in the14 tertiary pediatric hospitals across Canada. The survey included an initial scenario of pediatric TBI that evolved into three further scenarios. Each scenario had required responses and an embedded branching logic algorithm ascertaining clinical management. The survey instrument assimilated data about the importance of nonconvulsive status epilepticus and nonconvulsive seizures detection and treatment, and whether they are a cause of brain injury that adversely affects neurologic outcomes. Of the 79 specialists who replied (43% response rate), 68%-78% elected to order an electroencephalographic across all four scenarios, and one-third (31%-36%; scenario dependent) would request an urgent electroencephalographic (within the hour) in the comatose pediatric traumatic brain injury patient. In the absence of pharmacologic paralysis or intracranial pressure spikes, half-hour electroencephalographic (41%-55%) was preferred over ⩾24-h continuous electroencephalographic monitoring (29%-40%). Finally, nonconvulsive status epilepticus (81%-87%) and nonconvulsive seizures (61%-73%) were considered to be a cause of poor neurologic outcomes warranting aggressive pharmacologic management. The Canadian specialists' opinion is that nonconvulsive seizures and nonconvulsive status epilepticus are biomarkers of brain injury and contribute to worsened outcomes. This suggests the urgency of future outcome
Joffe, Ari R; Bowman, Stephen M; Richer, Lawrence
Objectives: It remains uncertain whether nonconvulsive seizures and nonconvulsive status epilepticus in pediatric traumatic brain injury are deleterious to the brain and/or impact the recovery from injury. Consequently, optimal electroencephalographic surveillance and management is unknown. We aimed to determine specialists’ opinion regarding the detection and treatment of nonconvulsive seizures or nonconvulsive status epilepticus in pediatric traumatic brain injury, regardless of their practice. Methods: In 2012, 183 surveys were sent to all 93 neurologists, 27 neurosurgeons, and 63 intensivists in the14 tertiary pediatric hospitals across Canada. The survey included an initial scenario of pediatric TBI that evolved into three further scenarios. Each scenario had required responses and an embedded branching logic algorithm ascertaining clinical management. The survey instrument assimilated data about the importance of nonconvulsive status epilepticus and nonconvulsive seizures detection and treatment, and whether they are a cause of brain injury that adversely affects neurologic outcomes. Results: Of the 79 specialists who replied (43% response rate), 68%–78% elected to order an electroencephalographic across all four scenarios, and one-third (31%–36%; scenario dependent) would request an urgent electroencephalographic (within the hour) in the comatose pediatric traumatic brain injury patient. In the absence of pharmacologic paralysis or intracranial pressure spikes, half-hour electroencephalographic (41%–55%) was preferred over ⩾24-h continuous electroencephalographic monitoring (29%–40%). Finally, nonconvulsive status epilepticus (81%–87%) and nonconvulsive seizures (61%–73%) were considered to be a cause of poor neurologic outcomes warranting aggressive pharmacologic management. Conclusion: The Canadian specialists’ opinion is that nonconvulsive seizures and nonconvulsive status epilepticus are biomarkers of brain injury and contribute to
Epstein, Daniel; Diu, Eric; Abeysekera, Tamara; Kam, Daniel; Chan, Yin
Non-convulsive status epilepticus can result in significant morbidity and mortality. The condition can be difficult to recognise, and can mimic delirium due to other underlying pathologies. There are several clinical subtypes, although these can be difficult to distinguish by their clinical features alone. Electroencephalogram is the key diagnostic tool to making the diagnosis, but this investigation is a limited resource in many institutions. In this review, we present a case of non-convulsive status epilepticus, manifesting as delirium, and then proceed to a literature review on this important diagnosis.
Reznik, Michael E.; Berger, Karen; Claassen, Jan
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
Jeong, Anna; Strahle, Jennifer; Vellimana, Ananth K; Limbrick, David D; Smyth, Matthew D; Bertrand, Mary
OBJECTIVE Electrical status epilepticus of sleep (ESES) is a rare electrographic pattern associated with global regression, which is often poorly responsive to traditional epilepsy treatments and can have a devastating and permanent neurocognitive outcome. The authors analyzed clinical, electroencephalographic, and neuropsychological outcomes in 9 patients with refractory ESES treated with functional hemispherotomy to illustrate the wide clinical spectrum associated with the disease and explore the role of hemispherotomy in its treatment. METHODS During the period between 2003 and 2015, 80 patients underwent hemispherotomy at the authors' institution. Video electroencephalography (EEG) reports were reviewed for ESES or continuous spikes and waves during sleep (CSWS). Patients with preoperative ESES (> 85% slow-wave sleep occupied by spike waves), a unilateral structural lesion amenable to surgery, and more than 6 months of follow-up data were included in the analysis. Clinical data, EEG recordings, neuropsychological testing, and parental and clinician reports were retrospectively reviewed. RESULTS Nine patients were eligible for study inclusion. Age at seizure onset ranged from birth to 4.2 years (mean 1.9 years), age at ESES diagnosis ranged from 3.5 to 8.8 years (mean 6.0 years), and age at hemispherotomy ranged from 3.7 to 11.5 years (mean 6.8 years). All patients had drug-resistant epilepsy. The duration of epilepsy prior to hemispherotomy ranged from 2.7 to 8.9 years (mean ± SD, 5.0 ± 2.2 years). Engel Class I seizure outcome was observed in all 9 children, with a mean follow-up of 3.0 years (range 0.5-6.1 years). Hemispherotomy terminated ESES in 6 of 6 patients with available postoperative sleep EEG. All children had preoperative neuropsychological impairments. Developmental regression was halted postoperatively, but none of the children returned to their original pre-ESES baseline. Four children demonstrated academic gains, 2 of whom transitioned to
Gaspard, Nicolas; Foreman, Brandon P; Alvarez, Vincent; Cabrera Kang, Christian; Probasco, John C; Jongeling, Amy C; Meyers, Emma; Espinera, Alyssa; Haas, Kevin F; Schmitt, Sarah E; Gerard, Elizabeth E; Gofton, Teneille; Kaplan, Peter W; Lee, Jong W; Legros, Benjamin; Szaflarski, Jerzy P; Westover, Brandon M; LaRoche, Suzette M; Hirsch, Lawrence J
The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale). Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes. Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation. © 2015 American Academy of Neurology.
Sonneville, Romain; Mariotte, Eric; Neuville, Mathilde; Minaud, Sébastien; Magalhaes, Eric; Ruckly, Stéphane; Cantier, Marie; Voiriot, Guillaume; Radjou, Aguila; Smonig, Roland; Soubirou, Jean-François; Mourvillier, Bruno; Bouadma, Lila; Wolff, Michel; Timsit, Jean-François
Abstract Status epilepticus (SE) is a common complication of acute encephalitis, but its determinants and prognostic value in this setting are not known. Risk factors for early-onset SE (within 48 hours of intensive care unit [ICU] admission) in consecutive adult patients with all-cause encephalitis admitted to the medical ICU of a university hospital (1991–2013) were evaluated by multivariate logistic regression analysis. To examine the prognostic value of SE, patients were classified into 3 groups: no SE, nonrefractory SE (NRSE), and refractory SE (RSE). Poor neurologic outcome was defined by a modified Rankin score of 4 to 6. Among the 290 patients, 58 (20%, 95% CI: 15%–25%) developed early-onset SE, comprising 44 patients with NRSE and 14 patients with RSE. Coma (adjusted odds ratio [OR]: 3.1, 95% CI: 1.5–6.3), cortical lesions on neuroimaging (adjusted OR: 3.7, 95% CI: 1.8–7.8), and nonneurologic organ failure(s) (adjusted OR: 13.6, 95% CI: 4.9–37.7) were found to be independent risk factors for SE. By contrast, a bacterial etiology had a protective effect (adjusted OR: 0.3, 95% CI: 0.1–0.7). Age, body temperature, and blood sodium levels were not independently associated with SE. Poor neurologic outcomes were observed at day 90 in respectively 23% (95% CI: 17%–28%), 23% (95% CI: 10%–35%), and 71% (95% CI: 48%–95%) of no SE, NRSE, and RSE patients (P < 0.01). After adjusting for confounders, RSE, but not NRSE, remained independently associated with 90-day mortality (adjusted OR: 6.0, 95% CI: 1.5–23.3). Coma, cortical involvement on neuroimaging, and nonneurologic organ failure(s) are independent risk factors for SE in patients with acute encephalitis. Conversely, a bacterial etiology is associated with a lower risk of SE. These findings may help identify patients who may benefit from prophylactic antiepileptic drugs. PMID:27472682
Hocker, Sara; Nagarajan, Elanagan; Rabinstein, Alejandro A; Hanson, Dennis; Britton, Jeffrey W
Prolonged seizures in super-refractory status epilepticus (SRSE) have been shown to cause neuronal death and reorganization, and visual inspection in individual case studies has demonstrated progressive cortical and subcortical atrophy. At present, magnetic resonance imaging (MRI) studies that evaluate brain atrophy in SRSE are lacking. To document and quantify the development of atrophy over time in SRSE. This retrospective medical record review included all patients with SRSE who were admitted to a tertiary referral campus of the Mayo Clinic Hospital with SRSE from January 1, 2001, to December 31, 2013. Patients with (1) an initial MRI scan performed within 2 weeks of SRSE onset, (2) a second MRI scan within 6 months of SRSE resolution, and (3) a minimum duration of 1 week between MRI scans were included. The ventricular brain ratio (VBR) was measured on T2-weighted fluid-attenuated inversion recovery (FLAIR) images at disease onset and during follow-up. Measurements were performed on axial FLAIR images with section thickness of less than 5 mm. The plane immediately superior to the caudate head was chosen for analysis. The hypothesis that atrophy develops during SRSE despite seizure control (electroencephalogram background suppression with anesthetic drugs) was tested. Data were analyzed from June 1 to December 31, 2015. Change in VBR (ΔVBR) as a percentage of the starting measure. Nineteen patients met the inclusion criteria; these included 10 men (53%) and 9 women (47%) with a median age of 41 (interquartile range [IQR], 25-68) years. Anesthetic agents were required for a median of 13 (IQR, 5-37) days. Initial MRI was performed a median of 2 (IQR, 1-7.5) days from the onset of SRSE, and the second MRI was performed a median of 11 (IQR, 5-15.5) days from the resolution of SRSE, with a median of 40 (IQR, 15-65) days between MRI scans. Median ΔVBR was 23.3% (IQR, 10.5%-70.3%). A significant correlation between the duration of anesthetic agent use and ΔVBR was
McClelland, Andrew C.; Gomes, William A.; Shinnar, Shlomo; Hesdorffer, Dale C; Bagiella, Emilia; Lewis, Darrell V; Bello, Jacqueline A; Chan, Stephen; MacFall, James; Chen, Min; Pellock, John M; Nordli, Douglas R; Frank, L. Mathew; Moshe, Solomon; Shinnar, Ruth C; Sun, Shumei
Purpose The pathogenesis of febrile status epilepticus is poorly understood, but prior studies suggest an association with temporal lobe abnormalities including hippocampal malrotation. We employ a quantitative morphometric method to assess the association between temporal lobe morphology and febrile status epilepticus. Methods Brain MR imaging was obtained in children presenting with febrile status epilepticus and control subjects as part of the FEBSTAT study. Medial temporal lobe morphologic parameters were measured manually, including distance of the hippocampus from midline, hippocampal height:width ratio, hippocampal angle, collateral sulcus angle, and width of the temporal horn. Results Temporal lobe morphologic parameters are correlated with presence of visual hippocampal malrotation; the strongest association is with left temporal horn width (p < 0.001, Adjusted OR 10.59). Multiple morphologic parameters correlate with febrile status epilepticus, encompassing both right and left sides. This association is statistically strongest in the right temporal lobe, whereas hippocampal malrotation is almost exclusively left-sided in this cohort. The association between temporal lobe measurements and febrile status epilepticus persists when the analysis is restricted to cases with visually normal imaging without hippocampal malrotation or other visually apparent abnormality. Conclusions Several component morphological features of hippocampal malrotation are independently associated with febrile status epilepticus, even when complete hippocampal malrotation is absent. Unexpectedly, this association predominantly involves the right temporal lobe. These findings suggest that a spectrum of bilateral temporal lobe anomalies are associated with febrile status epilepticus in children. Hippocampal malrotation may represent a visually apparent subset of this spectrum. PMID:27633809
Körtvelyessy, Peter; Huchtemann, Tessa; Heinze, Hans-Jochen; Bittner, Daniel M
The current knowledge about neuroprotective mechanisms in humans after status epilepticus is scarce. One reason is the difficulty to measure possible mediators of these neuroprotective mechanisms. The dawn of microRNA detection in the cerebrospinal fluid (CSF) and the recent advancements in measuring proteins in the CSF such as progranulin, which is, e.g., responsible for neurite outgrowth and limiting exceeding neuroinflammatory responses, have given us new insights into putative neuroprotective mechanisms following status epilepticus. This should complement the animal data. In this review, we cover what is known about the role of progranulin as well as the links between microRNA changes and the progranulin pathway following status epilepticus in humans and animals hypothesizing neuroprotective and neurorehabilitative effects. Progranulin has also been found to feature prominently in the neuroprotective processes under hypoxic conditions and initiating neurorehabilitative processes. These properties may be used therapeutically, e.g., through drugs that raise the progranulin levels and therefore the cerebral progranulin levels as well with the goal of improving the outcome after status epilepticus.
Dunleavy, Mark; Shinoda, Sachiko; Schindler, Clara; Ewart, Claire; Dolan, Ross; Gobbo, Oliviero L.; Kerskens, Christian M.; Henshall, David C.
Hippocampal sclerosis is a common pathological finding in patients with temporal lobe epilepsy, including children, but a causal relationship to early-life seizures remains in question. Neonatal status epilepticus in animals can result in neuronal death within the hippocampus, although macroscopic features of hippocampal shrinkage are not evident at adulthood. Here, we examined electrophysiological and pathological consequences of focally evoked status epilepticus triggered by intra-amygdala microinjection of kainic acid in postnatal day 10 rat pups. Neonatal status epilepticus resulted in extensive neuronal death in the ipsilateral hippocampal CA1 and CA3 subfields and hilus, as assessed by DNA fragmentation and Fluoro-Jade B staining 72 hours later. The contralateral hippocampus was not significantly damaged. Histopathology at P55/P65 revealed unilateral hippocampal sclerosis (grade IV, modified Wyler/Watson scale) comprising >50% CA1 and CA3 neuron loss and astrogliosis. Additional features included hydrocephalus ex vacuo, modest dentate granule cell layer widening, and altered neuropeptide Y immunoreactivity indicative of synaptic rearrangement. Hippocampal atrophy was also evident on magnetic resonance imaging. Depth electrode recordings at adulthood detected spontaneous seizures that involved the ipsilateral hippocampus and amygdala. A significant positive correlation was found between hippocampal pathology grade and both frequency and duration of epileptic seizures at adulthood. The current study demonstrates that experimental neonatal status epilepticus can result in classical unilateral hippocampal sclerosis and temporal lobe epilepsy. PMID:19948825
Ferlisi, M; Hocker, S; Grade, M; Trinka, E; Shorvon, S
The treatment of refractory and super refractory status epilepticus is a "terra incognita" from the point of view of evidence-based medicine. As randomized or controlled studies that are sufficiently powered are not feasible in relation to the many therapies and treatment approaches available, we carried out an online multinational audit (registry) in which neurologists or intensivists caring for patients with status epilepticus may prospectively enter patients who required general anesthesia to control the status epilepticus (SE). To date, 488 cases from 44 different countries have been collected. Most of the patients had no history of epilepsy and had a cryptogenic etiology. First-line treatment was delayed and not in line with current guidelines. The most widely used anesthetic of first choice was midazolam (59%), followed by propofol and barbiturates. Ketamine was used in most severe cases. Other therapies were administered in 35% of the cases, mainly steroids and immunotherapy. Seizure control was achieved in 74% of the patients. Twenty-two percent of patients died during treatment, and four percent had treatment actively withdrawn because of an anticipated poor outcome. The neurological outcome was good in 36% and poor in 39.3% of cases, while 25% died during hospitalization. Factors that positively influenced outcome were younger age, history of epilepsy, and low number of different anesthetics tried. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015. Published by Elsevier Inc.
Liu, Gumei; Gu, Bin; He, Xiao-Ping; Joshi, Rasesh B; Wackerle, Harold D; Rodriguiz, Ramona Marie; Wetsel, William C; McNamara, James O
Temporal lobe epilepsy is the most common and often devastating form of human epilepsy. The molecular mechanism underlying the development of temporal lobe epilepsy remains largely unknown. Emerging evidence suggests that activation of the BDNF receptor TrkB promotes epileptogenesis caused by status epilepticus. We investigated a mouse model in which a brief episode of status epilepticus results in chronic recurrent seizures, anxiety-like behavior, and destruction of hippocampal neurons. We used a chemical-genetic approach to selectively inhibit activation of TrkB. We demonstrate that inhibition of TrkB commencing after status epilepticus and continued for 2 weeks prevents recurrent seizures, ameliorates anxiety-like behavior, and limits loss of hippocampal neurons when tested weeks to months later. That transient inhibition commencing after status epilepticus can prevent these long-lasting devastating consequences establishes TrkB signaling as an attractive target for developing preventive treatments of epilepsy in humans. Copyright © 2013 Elsevier Inc. All rights reserved.
Körtvelyessy, Peter; Huchtemann, Tessa; Heinze, Hans-Jochen; Bittner, Daniel M.
The current knowledge about neuroprotective mechanisms in humans after status epilepticus is scarce. One reason is the difficulty to measure possible mediators of these neuroprotective mechanisms. The dawn of microRNA detection in the cerebrospinal fluid (CSF) and the recent advancements in measuring proteins in the CSF such as progranulin, which is, e.g., responsible for neurite outgrowth and limiting exceeding neuroinflammatory responses, have given us new insights into putative neuroprotective mechanisms following status epilepticus. This should complement the animal data. In this review, we cover what is known about the role of progranulin as well as the links between microRNA changes and the progranulin pathway following status epilepticus in humans and animals hypothesizing neuroprotective and neurorehabilitative effects. Progranulin has also been found to feature prominently in the neuroprotective processes under hypoxic conditions and initiating neurorehabilitative processes. These properties may be used therapeutically, e.g., through drugs that raise the progranulin levels and therefore the cerebral progranulin levels as well with the goal of improving the outcome after status epilepticus. PMID:28245590
Propofol infusion syndrome (PRIS) is a fatal complication when doses of propofol administration exceed 4 mg/kg/h for more than 48 hours. Propofol overdosage is not uncommon in patients with refractory status epilepticus (RSE). We describe a case of refractory status epilepticus complicated by propofol infusion syndrome and collect from 5 databases all reports of refractory status epilepticus cases that were treated by propofol and developed the syndrome and outline whether refractory status epilepticus treatment with propofol is standardized according to international recommendations, compare it with alternative medications, and discuss how this syndrome can be treated and prevented. A total of 21 patients who developed this syndrome reported arrhythmia in all cases (100%), rhabdomyolysis in 9 cases (42%), lactic acidosis in 13 cases (62%), renal failure in 8 cases (38%), lipemia in 7 cases (33%), and elevated hepatic enzymes in 6 cases (28%). 13 patients died (66%). Propofol is still given in a dosage higher than what is internationally recommended, and new treatment modalities such as renal replacement therapy, blood exchange, and extracorporeal membrane oxygenation seem to be promising. In conclusion, propofol should be carefully titrated, the maximal infusion rate needs to be reassessed, and combination of different sedative agents may be considered. PMID:27493812
Sahin, Mustafa; Menache, Caroline C; Holmes, Gregory L; Riviello, James J
High-dose suppressive therapy (HDST) is used to treat refractory status epilepticus (RSE). Prolonged therapy is required in some cases, and prognosis is important in making therapeutic decisions. The authors therefore studied the long-term outcome in previously normal children who survived prolonged HDST for acute symptomatic RSE. All have intractable epilepsy, and none returned to baseline.
McVicar, Kathryn A.; Shinnar, Shlomo
The Landau-Kleffner syndrome (LKS) and electrical status epilepticus in slow wave sleep (ESES) are rare childhood-onset epileptic encephalopathies in which loss of language skills occurs in the context of an epileptiform EEG activated in sleep. Although in LKS the loss of function is limited to language, in ESES there is a wider spectrum of…
McVicar, Kathryn A.; Shinnar, Shlomo
The Landau-Kleffner syndrome (LKS) and electrical status epilepticus in slow wave sleep (ESES) are rare childhood-onset epileptic encephalopathies in which loss of language skills occurs in the context of an epileptiform EEG activated in sleep. Although in LKS the loss of function is limited to language, in ESES there is a wider spectrum of…
Igarashi, Ayuko; Okumura, Akihisa; Komatsu, Mitsutaka; Tomita, Osamu; Abe, Shinpei; Ikeno, Mitsuru; Saito, Masako; Nakazawa, Tomoyuki; Shimizu, Toshiaki
We describe the clinical course and amplitude-integrated EEG findings in three children with non-accidental head injury and discuss on the importance of continuous aEEG monitoring in infants. NCSE was defined as a continuous 30-min seizure or briefer seizures occurring consecutively comprising at least 30 min of any 1-h period. Non-accidental head injury was diagnosed on the basis of neuroimaging findings such as subdural hemorrhage. Antiepileptic treatment was performed with continuous amplitude-integrated EEG monitoring. The age of the patients ranged from 48 days to nine months. All of them had loss of consciousness and seizures on presentation. Nonconvulsive status epilepticus without clinical symptoms were recognized in all patients. Vigorous antiepileptic treatment against nonconvulsive status epilepticus was made in two patients, whereas nonconvulsive status epilepticus disappeared within one hour without additional treatment in one. Our experience indicates that nonconvulsive status epilepticus were not uncommon in children with non-accidental head injury. Continuous amplitude-integrated EEG monitoring will be one of the useful methods in encephalopathic children in order to estimate seizure burden objectively and to treat seizures appropriately. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Keros, Sotirios; Buraniqi, Ersida; Alex, Byron; Antonetty, Annalee; Fialho, Hugo; Hafeez, Baria; Jackson, Michele C; Jawahar, Rachel; Kjelleren, Stephanie; Stewart, Elizabeth; Morgan, Lindsey A; Wainwright, Mark S; Sogawa, Yoshimi; Patel, Anup D; Loddenkemper, Tobias; Grinspan, Zachary M
Ketamine is an emerging therapy for pediatric refractory status epilepticus. The circumstances of its use, however, are understudied. The authors described pediatric refractory status epilepticus treated with ketamine from 2010 to 2014 at 45 centers using the Pediatric Hospital Inpatient System database. For comparison, they described children treated with pentobarbital. The authors estimated that 48 children received ketamine and pentobarbital for refractory status epilepticus, and 630 pentobarbital without ketamine. Those receiving only pentobarbital were median age 3 [interquartile range 0-10], and spent 30 [18-52] days in-hospital, including 17 [9-28] intensive care unit (ICU) days; 17% died. Median cost was $148 000 [81 000-241 000]. The pentobarbital-ketamine group was older (7 [2-11]) with longer hospital stays (51 [30-93]) and more ICU days (29 [20-56]); 29% died. Median cost was $298 000 [176 000-607 000]. For 71%, ketamine was given ≥1 day after pentobarbital. Ketamine cases per half-year increased from 2 to 9 ( P < .05). Ketamine is increasingly used for severe pediatric refractory status epilepticus, typically after pentobarbital. Research on its effectiveness is indicated.
Lin, Kuang-Lin; Wang, Huei-Shyong
Status epilepticus in childhood is more common, with a different range of causes and a lower risk of death, than convulsive status epilepticus in adults. Acute central nervous system infections appear to be markers for morbidity and mortality. Nevertheless, central nervous infection is usually presumed in these conditions. Many aspects of the pathogenesis of acute encephalitis and acute febrile encephalopathy with status epilepticus have been clarified in the past decade. The pathogenesis is divided into direct pathogens invasion or immune-mediated mechanisms. Over the past few decades, the number of antineuronal antibodies to ion channels, receptors, and other synaptic proteins described in association with central nervous system disorders has increased dramatically, especially their role in pediatric encephalitis and status epilepticus. These antineuronal antibodies are divided according to the location of their respective antigens: (1) intracellular antigens, including glutamic acid decarboxylase and classical onconeural antigens such as Hu (antineuronal nuclear antibody 1, ANNA1), Ma2, Yo (Purkinje cell autoantibody, PCA1), Ri (antineuronal nuclear antibody 2, ANNA2), CV2/CRMP5, and amphiphysin; and (2) cell membrane ion channels or surface antigens including voltage-gated potassium channel receptor, N-methyl-d-aspartate receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, γ-aminobutyric acid(B) receptor, leucine-rich glioma-inactivated protein 1, and contactin-associated protein-like 2. Identifying the mechanism of the disease may have important therapeutic implications. Copyright © 2013. Published by Elsevier B.V.
Komur, Mustafa; Arslankoylu, Ali Ertug; Okuyaz, Cetin; Keceli, Meryem; Derici, Didem
We investigated the etiology, treatment, and prognosis of patients treated for status epilepticus at a pediatric intensive care unit. Medical records of 89 patients admitted to a pediatric intensive care unit with status epilepticus were reviewed retrospectively. Patients ranged in age from 2 months to 18 years (mean age ± S.D., 4.7 ± 3.8 years). Seizure etiologies comprised remote symptomatic in 47 (52.7%), febrile in 15 (16.9%), acute symptomatic in 12 (13.5%), and unknown in 15 (16.9%). Seizure durations ranged from 30-60 minutes in 58 patients, whereas 31 manifested refractory seizures longer than 60 minutes. Seizure control was achieved within 30 minutes in 55 patients, from 30-60 minutes in 19, and after 60 minutes in 15. Rectal diazepam was administered to 38 (42.7%) patients before admission to the hospital. Length of intensive care unit stay increased with increasing seizure duration (P < 0.05). The total mortality rate was 3.4%. This lower mortality rate may be considered evidence of the effectiveness and reliability of the status epilepticus treatment protocol in our pediatric intensive care unit. Prehospital rectal diazepam administration and the treatment of brain edema in the intensive care unit may be useful in the management of patients with status epilepticus. Copyright © 2012 Elsevier Inc. All rights reserved.
Francois, Densley; Roberts, Jessica; Hess, Stephany; Probst, Luke; Eksioglu, Yaman
Oral diazepam, administered in varying doses, is among the few proposed treatment options for electrical status epilepticus during slow wave sleep in children. We sought to retrospectively evaluate the long-term efficacy of high-dose oral diazepam in reducing electrographic and clinical evidence of electrical status epilepticus during slow wave sleep in children. Additionally, we surveyed caregivers to assess safety and behavioral outcomes related to ongoing therapy. We collected demographic and clinical data on children treated for electrical status epilepticus during slow wave sleep between October 2010 and March 2013. We sought to identify the number of patients who achieved at least a 50% reduction in spike wave index on electroencephalograph after receiving high-dose oral diazepam. We also administered a questionnaire to caregivers to assess for behavioral problems and side effects. We identified 42 evaluable patients who received high-dose diazepam (range 0.23-2.02 mg/kg per day) to treat electrical status epilepticus during slow wave sleep. Twenty-six patients had spike reduction data and 18/26 (69.2%) children achieved a greater than 50% reduction in spike wave count from an average of 15.54 to 5.05 (P = 0.001). We received 28 responses to the questionnaire. Some patients experienced new onset of difficulties with problem-solving and speech and writing development. Sleep disturbances (50%) and irritability (57.1%) were the most frequent side effects reported. There did not appear to be a dose-related effect with electroencephalograph changes, behavioral effects, or side effects. High-dose oral diazepam significantly reduces the spike wave count on electroencephalograph in children with electrical status epilepticus during slow wave sleep. Although this therapy improves electroencephalograph-related findings, it can be associated with concerning neurological and behavioral side effects in some individuals, so further study is warranted. Copyright © 2014
Lyons, Todd W.; Johnson, Kara B.; Michelson, Kenneth A.; Nigrovic, Lise E.; Loddenkemper, Tobias; Prabhu, Sanjay P.; Kimia MD, Amir A.
PURPOSE To determine the yield of emergent neuroimaging among children with new-onset seizures presenting with status epilepticus. METHOD We performed a cross-sectional study of children seen at a single ED between 1995–2012 with new-onset seizure presenting with status epilepticus. We defined status epilepticus as a single seizure or multiple seizures without regaining consciousness lasting 30 minutes or longer. Our primary outcome was urgent or emergent intracranial pathology identified on neuroimaging. We categorized neuroimaging results as emergent if they would have changed acute management as assessed by a blinded neuroradiologist and neurologist. To ensure abnormalities were not missed, we review neuroimaging results for 30 days following the initial episode of SE. RESULTS We included 177 children presenting with new-onset seizure with status epilepticus, of whom 170 (96%) had neuroimaging performed. Abnormal findings were identified on neuroimaging in 64/177 (36%, 95% confidence interval 29–43%) children with 15 (8.5%, 95% confidence interval 5.2–14%) children having urgent or emergent pathology. Four (27%) of the 15 children with urgent or emergent findings had a normal non-contrast computed tomography scan and a subsequently abnormal magnetic resonance image. Longer seizure duration and older age were associated with urgent or emergent intracranial pathology. CONCLUSION A substantial minority of children with new-onset seizures presenting with status epilepticus have urgent or emergent intracranial pathology identified on neuroimaging. Clinicians should strongly consider emergent neuroimaging in these children. Magnetic resonance imaging is the preferred imaging modality when available and safe. PMID:26773658
Lyons, Todd W; Johnson, Kara B; Michelson, Kenneth A; Nigrovic, Lise E; Loddenkemper, Tobias; Prabhu, Sanjay P; Kimia, Amir A
To determine the yield of emergent neuroimaging among children with new-onset seizures presenting with status epilepticus. We performed a cross-sectional study of children seen at a single ED between 1995 and 2012 with new-onset seizure presenting with status epilepticus. We defined status epilepticus as a single seizure or multiple seizures without regaining consciousness lasting 30 min or longer. Our primary outcome was urgent or emergent intracranial pathology identified on neuroimaging. We categorized neuroimaging results as emergent if they would have changed acute management as assessed by a blinded neuroradiologist and neurologist. To ensure abnormalities were not missed, we review neuroimaging results for 30 days following the initial episode of SE. We included 177 children presenting with new-onset seizure with status epilepticus, of whom 170 (96%) had neuroimaging performed. Abnormal findings were identified on neuroimaging in 64/177 (36%, 95% confidence interval 29-43%) children with 15 (8.5%, 95% confidence interval 5.2-14%) children having urgent or emergent pathology. Four (27%) of the 15 children with urgent or emergent findings had a normal non-contrast computed tomography scan and a subsequently abnormal magnetic resonance image. Longer seizure duration and older age were associated with urgent or emergent intracranial pathology. A substantial minority of children with new-onset seizures presenting with status epilepticus have urgent or emergent intracranial pathology identified on neuroimaging. Clinicians should strongly consider emergent neuroimaging in these children. Magnetic resonance imaging is the preferred imaging modality when available and safe. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Dhote, Franck; Carpentier, Pierre; Barbier, Laure; Peinnequin, André; Baille, Valérie; Pernot, Fabien; Testylier, Guy; Beaup, Claire; Foquin, Annie; and others
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
Samala, Renato V; Parala-Metz, Armida; Davis, Mellar P
The search for an underlying cause of altered mental status not uncommonly becomes more challenging in the hospice and palliative care setting. Due to multiple coexisting conditions that affect mental status and shifting goals of care, discerning that single cause in this venue can become frustrating and even nonbeneficial at times. We present a case of nonconvulsive status epilepticus (NCSE), which multiple reports have shown to be a rarely contemplated cause of impaired consciousness. A concise review of NCSE follows, with emphasis on conditions that present similarly, precipitating factors, diagnostic and therapeutic considerations, and prognostic implications. Nonconvulsive status epilepticus is a reversible cause of altered consciousness, particularly when recognized promptly. In a palliative care unit, treatment should ultimately be guided by the patient's goals of care. © The Author(s) 2013.
Jabeen, S A; Cherukuri, Pavankumar; Mridula, Rukmini; Harshavardhana, K R; Gaddamanugu, Padmaja; Sarva, Sailaja; Meena, A K; Borgohain, Rupam; Jyotsna Rani, Y
To study the frequency, imaging characteristics, and clinical predictors for development of periictal diffusion weighted MRI abnormalities. We prospectively analyzed electro clinical and imaging characteristic of adult patients with cluster of seizures or status epilepticus between November 2013 and November 2015, in whom the diffusion weighted imaging was done within 24h after the end of last seizure (clinical or electrographic). There were thirty patients who fulfilled the inclusion and exclusion criteria. Twenty patients (66%) had periictal MRI abnormalities. Nine patients (34%) did not have any MRI abnormality. All the patients with PMA had abnormalities on diffusion weighted imaging (DWI). Hippocampal abnormalities were seen in nine (53%), perisylvian in two (11.7%), thalamic in five (30%), splenium involvement in two (11.7%) and cortical involvement (temporo-occipital, parieto-occipital, temporo-parietal, fronto-parietal and fronto-temporal) in sixteen (94.1%) patients. Complete reversal of DWI changes was noted in sixteen (80%) patients and four (20%) patients showed partial resolution of MRI abnormalities. Mean duration of seizures was significantly higher among patients with PMA (59.11+20.97h) compared to those without MRI changes (27.33+9.33h) (p<0.001). Diffusion abnormalities on MRI are common in patients with cluster of seizures and status epilepticus and were highly concordant with clinical semiology and EEG activity. Patients with longer duration of seizures/status were more likely to have PMA. Copyright © 2017 Elsevier B.V. All rights reserved.
Vieira, Michele Juliane; Perosa, Sandra Regina; Argañaraz, Gustavo Adolfo; Silva, José Antônio; Cavalheiro, Esper Abrão; da Graça Naffah-Mazzacoratti, Maria
OBJECTIVE: Refractory status epilepticus is one of the most life-threatening neurological emergencies and is characterized by high morbidity and mortality. Additionally, the use of anti-inflammatory drugs during this period is very controversial. Thus, this study has been designed to analyze the effect of a low dose of indomethacin (a COX inhibitor) on the expression of inflammatory molecules. METHOD: The hippocampus of rats submitted to pilocarpine-induced long-lasting status epilepticus was analyzed to determine the expression of inflammatory molecules with RT-PCR and immunohistochemistry. RESULTS: Compared with controls, reduced levels of the kinin B2 receptors IL1β and TNFα were found in the hippocampus of rats submitted to long-lasting status epilepticus and treated with indomethacin. CONCLUSIONS: These data show that low doses of indomethacin could be employed to minimize inflammation during long-lasting status epilepticus. PMID:25318094
Park, Hyeon-Mi; Noh, Young; Yang, Ji Won; Shin, Dong Hoon; Lee, Yeong-Bae
Cefepime-induced encephalopathy including nonconvulsive status epilepticus has been known to develop in the patients with renal impairment. However, we report a 74-year-old woman with normal renal function who developed stuporous mental status during cefepime administration. Electroencephalogram (EEG) revealed 2 Hz rhythmic sharp-and-waves continuously, which suggested nonconvulsive status epilepticus (NCSE). After cefepime discontinuation, clinical symptoms recovered gradually and EEG findings showed only background slowing without epileptiform discharges. Cefepime-induced NCSE could be developed even in the patients with normal renal function, when they are elderly. Therefore, clinicians should be aware of the possibility of cefepime-induced NCSE when prescribing cefepime even to the patients with normal renal function. PMID:28101482
Zeiler, F A; Matuszczak, M; Teitelbaum, J; Kazina, C J; Gillman, L M
Our goal was to perform a scoping systematic review of the literature on the use of plasmapheresis or plasma exchange (PE) for refractory status epilepticus (RSE) in adults. Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to May 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. Twenty-two original articles were identified. Twenty-seven adult patients were described in these articles, with a variety of autoimmune conditions leading to RSE. Seizure response with the application of PE therapy occurred in 14 of the 27 patients (51.9%), with 1 (3.7%) and 13 (48.1%) displaying partial and complete responses respectively. Generalized RSE was the most likely seizure subtype to respond to PE therapy. One patient had recorded an adverse events related to PE therapy. Oxford level 4, GRADE D evidence exists to suggest an uncertain response of adult autoimmune RSE to PE therapy. Thus, the routine application of PE therapy for adult autoimmune RSE cannot be recommended at this time. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Zeiler, F A; Matuszczak, M; Teitelbaum, J; Kazina, C J; Gillman, L M
Our goal was to perform a scoping systematic review of the literature on the use of plasmapheresis or plasma exchange (PE) for refractory status epilepticus (RSE) in children. Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to May 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. Twenty-two original articles were identified, with 37 pediatric patients. The mean age of the patients was 8.3 years (age median: 8.5, range: 0.6 years-17 years). Seizure response to PE therapy occurred in 9 of the 37 patients (24.3%) included in the review, with 7 patients (18.9%) displaying resolution of seizures and 2 patients (5.4%) displaying a partial reduction in seizure volume. Twenty-eight of the 37 patients (75.7%) had no response to PE therapy. No adverse events were recorded. Oxford level 4, GRADE D evidence exists to suggest little to no benefit of PE in pediatric RSE. Routine application of PE for pediatric RSE cannot be recommended at this time. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Valle-Dorado, María Guadalupe; Santana-Gómez, César Emmanuel; Orozco-Suárez, Sandra Adela; Rocha, Luisa
Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, γ-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ≤ 0.001) and glutamate (467%, p ≤ 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p < 0.001) and neuronal damage in dentate gyrus, CA1 and CA3. In contrast to SS-SE group, rats from the CG-SE group showed increased latency to the establishment of the status epilepticus (p = 0.048), absence of wet-dog shakes, reduced histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment. Copyright © 2015 Elsevier Ltd. All rights reserved.
Shatirishvili, Teona; Kipiani, Tamar; Lomidze, Giorgi; Gabunia, Maia; Tatishvili, Nino
Convulsive status epilepticus is the most common childhood neurological emergency in developing countries, where poor healthcare organisation could play a negative role in the management of the condition. Unavailability of second-line injectable anticonvulsants is an additional hindering factor in Georgia. This report reflects the results of the first study aimed at evaluating the epidemiological features of convulsive status epilepticus, as well as identifying obstacles influencing the management of patients with convulsive status epilepticus in Georgia. A prospective, hospital-based study was performed. Paediatric patients with convulsive status epilepticus, admitted to the emergency department of a referral academic hospital from 2007 to 2012, were included in the study. Forty-eight paediatric patients admitted to hospital met the criteria for convulsive status epilepticus. Seizure duration was significantly shorter among the group with adequate and timely pre-hospital intervention. Moreover, patients with appropriate pre-hospital treatment less frequently required mechanical ventilation (p=0.039). Four deaths were detected during the follow-up period, thus the case fatality rate was 8%. Only 31% of patients received treatment with intravenous phenytoin. The study results show that adequate and timely intervention could improve outcome of convulsive status epilepticus and decrease the need for mechanical ventilation. Mortality parameters were comparable to the results from other resource-limited countries. More than one third of patients did not receive appropriate treatment due to unavailability of phenytoin.
Kurz, J E; Sheets, D; Parsons, J T; Rana, A; Delorenzo, R J; Churn, S B
This study focused on the effects of status epilepticus on the activity of calcineurin, a neuronally enriched, calcium-dependent phosphatase. Calcineurin is an important modulator of many neuronal processes, including learning and memory, induction of apoptosis, receptor function and neuronal excitability. Therefore, a status epilepticus-induced alteration of the activity of this important phosphatase would have significant physiological implications. Status epilepticus was induced by pilocarpine injection and allowed to continue for 60 min. Brain region homogenates were then assayed for calcineurin activity by dephosphorylation of p-nitrophenol phosphate. A significant status epilepticus-dependent increase in both basal and Mn(2+)-dependent calcineurin activity was observed in homogenates isolated from the cortex and hippocampus, but not the cerebellum. This increase was resistant to 150 nM okadaic acid, but sensitive to 50 microM okadaic acid. The increase in basal activity was also resistant to 100 microM sodium orthovanadate. Both maximal dephosphorylation rate and substrate affinity were increased following status epilepticus. However, the increase in calcineurin activity was not found to be due to an increase in calcineurin enzyme levels. Finally, increase in calcineurin activity was found to be NMDA-receptor activation dependent. The data demonstrate that status epilepticus resulted in a significant increase in both basal and maximal calcineurin activity.
In the Lancet Neurology article “Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial” the authors conducted a prehospital, randomized controlled study to determine which treatment is more effective for status epilepticus (SE): benzodiazepine alone, or in combination with levetiracetam (LEV). Although the study had negative results, several aspects of the trial design likely masked any added effect that LEV may have had in controlling SE, including: higher doses of benzodiazepines, lower thresholds for determining cessation of SE, and a smaller sample size. Regardless, the study reaffirms the effectiveness and importance of early and adequate benzodiazepine dosing and helps guide us in designing future studies for treatment of SE. PMID:28090524
Gschwind, Markus; Foletti, Giovanni; Baumer, Alessandra; Bottani, Armand; Novy, Jan
Coffin-Lowry syndrome (CLS) is a rare neurodevelopmental condition caused by heterogeneous mutations in the RPS6KA3 gene on the X chromosome, leading to severe intellectual disability and dysmorphism in men, while women are carriers and only weakly affected. CLS is well known for stimulus-induced drop episodes; however, epilepsy is not commonly reported in this condition. We report on a CLS patient presenting with recurrent episodes of nonconvulsive status epilepticus (NCSE) with generalized epileptic activity, for which investigations did not find any other cause than the patient's genetic condition. This case underlines that the possibility of nonconvulsive epileptic seizures and status epilepticus should, therefore, be considered in those patients. The treatable diagnosis of NCSE may easily be overlooked, as symptoms can be unspecific.
Sutter, Raoul; Kaplan, Peter W
Proceeding from the proposed classification of status epilepticus syndromes by Shorvon in 1994, we performed a systematic search for reports presenting electroencephalography (EEG) patterns of nonconvulsive status epilepticus (NCSE) on all syndromes in the classification, where possible. Using the online medical search engine PubMed for 22 different search strategies, EEG patterns supporting a diagnosis of NCSE were sought. From a total of 4,328 search results, 123 cases with corresponding EEG patterns could be allocated to underlying epilepsy syndromes. Based on the characteristic EEG patterns found for the different NCSE syndromes, we present a synthesis of the significant EEG morphologies and evolutions in the individual NCSE syndromes. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
Zawar, Ifrah; Khan, Ashfa A; Sultan, Tipu; Rathore, Ahsan W
The Dyke-Davidoff-Masson Syndrome (DDMS) results from an insult to the growing brain in utero or early infancy, which lead to loss of neurons compromising the growth of the brain. Clinical presentation includes seizures, hemiparesis, facial asymmetry, and learning disability. Radiological findings include cerebral atrophy on one side. Here, we present a case with status epilepticus who had underlying DDMS. It is a rare syndrome and uncommon cause for status epilepticus. Infections of CNS, hypoxic ischemic encephalopathy, intracranial bleed, trauma, congenital vascular malformations are the common causes of this syndrome. Diagnosis is established after clinical history, examination, and MRI. Intractable seizures can be controlled with appropriate anticonvulsants. Subsequently, these children may require physiotherapy, speech therapy, and occupational therapy in addition to the anticonvulsant medication. Outcome is better if the seizures are controlled.
Shearer, Peter; Riviello, James
Generalized convulsive status epilepticus (GCSE) has a high morbidity and mortality, such that the rapid delivery of anticonvulsant therapy should be initiated within minutes of seizure onset to prevent permanent neuronal damage. GCSE is not a specific disease but is a manifestation of either a primary central nervous system (CNS) insult or a systemic disorder with secondary CNS effects. It is mandatory to look for an underlying cause. First-line therapies for seizures and status epilepticus include the use of a benzodiazepine, followed by an infusion of a phenytoin with a possible role for intravenous valproate or phenobarbital. If these first-line medications fail to terminate the GCSE, treatment includes the continuous infusion of midazolam, pentobarbital, or propofol.
Azar, Nabil J; Bangalore-Vittal, Nandakumar; Arain, Amir; Abou-Khalil, Bassel W
Nonconvulsive status epilepticus has been rarely reported with tiagabine (TGB) use. We report findings from continuous video-EEG monitoring and serial neurological examinations during prolonged episodes of stupor associated with TGB use in three patients who did not have epilepsy. All three patients had emergence of new type of events after starting TGB treatment. All three patients had gradual decline in responsiveness to verbal stimuli, intermittent twitching of the upper extremities, and urinary incontinence. The corresponding EEG showed gradual build-up of generalized bisynchronous delta-wave activity with subsequent intermingled sharp transients. Two patients did not respond to IV lorazepam, one of whom also did not respond to IV phenytoin. The EEG slowly normalized in conjunction with associated clinical improvement. Habitual seizures were found to be psychogenic, with no interictal evidence for epilepsy. Tiagabine-related stupor may represent a form of toxic encephalopathy in some cases rather than nonconvulsive status epilepticus. Copyright © 2013 Elsevier Inc. All rights reserved.
Nakae, Yoshiharu; Kudo, Yosuke; Yamamoto, Ryoo; Dobashi, Yuichi; Kawabata, Yuichi; Ikeda, Shingo; Yokoyama, Mutsumi; Higashiyama, Yuichi; Doi, Hiroshi; Johkura, Ken; Tanaka, Fumiaki
The aim of this study was to analyze the pattern of magnetic resonance diffusion-weighted imaging (DWI) findings in status epilepticus in terms of clinical characteristics. Participants comprised 106 patients with status epilepticus who were admitted to our hospital and underwent DWI. Forty-five patients (42.5 %) showed abnormal findings on DWI and were divided into two groups, comprising 26 patients (24.5 %) with cortex lesions alone and 19 patients (17.9 %) with cortex and pulvinar lesions in the same hemisphere. A long duration of status epilepticus (>120 min) tended to be more prevalent among patients with cortex and pulvinar lesions (57.9 %) than among patients with cortex lesions alone (30.8 %) by univariate and multivariate analyses. Todd's palsy tended to be more frequent in patients with abnormalities on DWI (24/45, 53.3 %) than in patients with normal DWI (21/61, 34.4 %). Six of the 26 patients with cortex lesions alone (23.1 %) had taken anti-epileptic drugs before the attack compared to none of the 19 patients with both cortex and pulvinar lesions. The trend toward a longer duration of status epilepticus in patients with both cortex and pulvinar lesions favors a spreading pattern of seizure discharge from cortex to pulvinar via cortico-pulvinar pathways, and anti-epileptic drugs might, to some extent, prevent spreading of seizure discharge from cortex to pulvinar. In addition, existence of high-intensity areas on DWI at the onset of epilepsy may be a predictive factor for the occurrence of Todd's palsy.
Giovannini, Giada; Monti, Giulia; Polisi, Michela M; Mirandola, Laura; Marudi, Andrea; Pinelli, Giovanni; Valzania, Franco; Girardis, Massimo; Nichelli, Paolo F; Meletti, Stefano
Refractory status epilepticus (RSE) is a particular critical condition characterized by seizures that continue despite the use of first- and second-line therapies and by high mortality. To date, only one prospective study investigated clinical features and prognostic factors in RSE. In this study, we performed a one-year prospective survey to identify clinical features, outcomes, and variables associated with the development of RSE in the adolescent and adult population of Modena, northern Italy. We observed 83 episodes of SE in 83 patients. In 31% of the cases, third-line therapy (anesthetic drug) was needed. Among this group, 14% resolved and were classified as RSE, while, in 17%, seizures recurred at withdrawal of anesthetics and were classified as super-RSE. The development of RSE/super-RSE was associated with a stuporous/comatose state at presentation and with the absence of a previous history of epilepsy. Refractory status epilepticus/super-refractory status epilepticus showed a worse outcome compared with responsive SE: 54% versus 21% for 30-day mortality; 19% versus 56% for a return to baseline condition. This prospective study confirms stupor/coma at onset as a relevant clinical factor associated with SE refractoriness. We observed a rate of RSE comparable with previous reports, with high mortality and morbidity. Mortality in the observed RSE was higher than in previous studies; this result is probably related to the low rate of a previous epilepsy history in our population that reflects a high incidence of acute symptomatic etiologies, especially the inclusion of patients with postanoxic SE who have a bad prognosis per se. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.
Belluzzo, Marco; Furlanis, Giovanni; Stragapede, Lara; Monti, Fabrizio
pre-morbid patient conditions and hospitalization complications possibly play a role in status epilepticus short-term outcome, although evidence is incomplete and non-conclusive. The study's aim was to define whether comorbidities and in-hospital complications arising after status epilepticus affect its prognosis. A retrospective single center study was carried out. All selected patients were adults presenting an EEG-proven status epilepticus episode between 2003 and 2014. Medical charts were comprehensively reviewed. In-hospital mortality and length of hospital stay represented study outcomes. One hundred seventy-three subjects met the inclusion criteria. Seventy-one cases (41%) developed infections and 59 (34%) non-infectious complications. Median hospital stay was 16days and overall in-hospital mortality was 44%. Multivariate analysis revealed the association between in-hospital mortality and the following comorbidities: history of diabetes mellitus (Odds ratio=7.89, p=0.002) and evidence of extracranial malignancy (Odds ratio=10.28, p=0.009). Complications were not associated to death after multivariate statistics, which instead displayed systemic inflammatory response syndrome significance (Odds ratio=12.90, p<0.001). Infections and non-infectious complications were associated with longer hospital stay (p=0.025 and p=0.01 respectively). status epilepticus management is a multifaceted problem. suggest that some pre-morbid patient conditions and in-hospital adverse events play an unfavorable prognostic role. This preliminary information may help clinicians optimize preventive and therapeutic strategies to guarantee patients the best chances of survival. Copyright © 2016 Elsevier B.V. All rights reserved.
Newey, Christopher R.; Wisco, Dolora; Nattanmai, Premkumar; Sarwal, Aarti
Background: Refractory status epilepticus is often treated with third-line therapy, such as pentobarbital coma. However, its use is limited by side effects. Recognizing and preventing major and minor adverse effects of prolonged pentobarbital coma may increase good outcomes. This study retrospectively reviewed direct and indirect medical and surgical pentobarbital coma. Methods: Retrospective chart review of all patients with refractory status epilepticus treated with pentobarbital over a 1 year period at a large tertiary care center. We collected baseline data, EEG data, and complications that were observed. Results: Overall, nine patients [median age 46.4 (IQR 21.7, 75.5) years] were induced with pentobarbital coma median 11 (IQR 3, 33) days after seizure onset for a median of 9 (IQR 3.5, 45.4) days. A total of four to eight concurrent antiepileptics were tried prior to the pentobarbital coma. Phenobarbital, due to recurrence of seizures on weaning pentobarbital coma, was required in seven patients. Observed complications included peripheral neuropathy (77.8%), cerebral atrophy (33.3%), volume overload (44.4%), renal/metabolic (77.8%), gastrointestinal (66.6%), endocrine (55.6%), cardiac/hemodynamic/vascular (77.8%), respiratory (100%), and infectious (77.8%). The number of complications trended with duration of induced coma but was nonsignificant. Median ICU length of stay was 40 (IQR 28, 97.5) days. Overall, five patients were able to follow commands after a median 37 (IQR 25.5, 90) days from coma onset. There were eight patients that were discharged from hospital with three remaining in a prolonged unresponsive state. There was one patient that died prior to discharge. Conclusions: This study highlights the high morbidity in patients with refractory status epilepticus requiring pentobarbital coma. Anticipating and addressing the indirect and direct complications in prolonged pentobarbital coma may improve survival and functional outcomes in patients with
Ermolenko, N A; Ermakov, A Iu; Buchneva, I A; Zakharova, E I; Kalikina, T A
We studied 52 patients with electric status epilepticus in slow sleep (EESSS) during 3-5 years. Age-dependent peculiarities of clinical course of the disease, risk factors for EESSS and rational approaches to antiepileptic treatment for these cases were singled out. Symptomatic and idiopathic EESSS variants were revealed. Combinations of valproates, levetiracetam and ethosuximidum were the most effective antiepileptic drugs in the treatment of EESSS.
Dubey, Deepanshu; Bhoi, Sanjeev K; Kalita, Jayantee; Misra, Usha K
Refractory status epilepticus (RSE) can influence the outcome of status epilepticus (SE). In the present study, we report the aetiology and predictors of outcomes of RSE in a developing country. This is a prospective hospital-based study of SE patients (continuous seizures for five minutes or more). Those who had SE persisting after two antiepileptic drugs were defined as having RSE. We present the demographic information, duration, and type of SE, and we note its severity using the status epilepticus severity score (STESS), its aetiology, comorbidities and imaging findings. The outcome of RSE was defined as cessation of seizures and the condition upon discharge, as assessed by the modified Rankin Scale. A total of 35 (42.5%) of our 81 patients had RSE. The median duration of SE before starting treatment was 2 hours (range=0.008-160 h). The most common causes of RSE were stroke in 5 (14.3%), central nervous system (CNS) infections in 12 (34.3%) and metabolic encephalopathies in 13 (37.1%) patients. Some 21 (60%) patients had comorbidities, and the STESS was favourable in 7 (20%) patients. A total of 14 (20%) patients died, but death was directly related to SE in only one of these. Some 10 patients had super-refractory status epilepticus, which was due to CNS infection in 5 (50%) and metabolic encephalopathy in 3 (30%). On multivariate analysis, an unfavourable STESS (p=0.05) and duration of SE before treatment (p=0.01) predicted RSE. Metabolic aetiology (p=0.05), mechanical ventilation (p60 years (p=0.003) were predictors of poor outcomes. RSE was common (42.5%) among patients with SE in a tertiary care center in India. It was associated with high mortality and poor outcomes. Age above 60 years and metabolic aetiology were found to be predictors of poor outcomes.
Basic research is mostly focused on the consequences of status epilepticus (SE) in terms of neuronal loss, behavior, epileptogenesis or disease-modifying effects such as preventing epilepsy or reducing seizure severity. Among the drugs tested, several were able to trigger neuroprotection but only a few had disease-modifying effects. At this point, many data are still missing, namely which drugs could efficiently stop SE or which mechanisms of action should be searched for to prevent the harmful consequences of SE.
Kaminski, Rafal M. . E-mail: email@example.com; Blaszczak, Piotr; Dekundy, Andrzej; Parada-Turska, Jolanta; Calderazzo, Lineu; Cavalheiro, Esper A.; Turski, Waldemar A.
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.
Kaminski, Rafal M; Blaszczak, Piotr; Dekundy, Andrzej; Parada-Turska, Jolanta; Calderazzo, Lineu; Cavalheiro, Esper A; Turski, Waldemar A
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.
Chang, Pishan; Walker, Matthew C
Mossy fiber to CA3 synapses exhibit metaplasticity during the development of epilepsy, and valproate in control animals can modulate long-term plasticity at this synapse. Here we show that valproate alters frequency facilitation (short-term plasticity) at this synapse in hippocampal slices from post-status epilepticus but not control animals. This indicates that valproate can have specific actions in the "epileptic" brain.
El Houssaini, Kenza; Ivanov, Anton I.; Bernard, Christophe; Jirsa, Viktor K.
Epilepsy, refractory status epilepticus, and depolarization block are pathological brain activities whose mechanisms are poorly understood. Using a generic mathematical model of seizure activity, we show that these activities coexist under certain conditions spanning the range of possible brain activities. We perform a detailed bifurcation analysis and predict strategies to escape from some of the pathological states. Experimental results using rodent data provide support of the model, highlighting the concept that these pathological activities belong to the endogenous repertoire of brain activities.
Nagase, Hiroaki; Nishiyama, Masahiro; Nakagawa, Taku; Fujita, Kyoko; Saji, Yohsuke; Maruyama, Azusa
We conducted a retrospective study to compare the outcome of intravenous midazolam infusion without electroencephalography or targeted temperature management and barbiturate coma therapy with electroencephalography and targeted temperature management for treating convulsive refractory febrile status epilepticus. Of 49 consecutive convulsive refractory febrile status epilepticus patients admitted to the pediatric intensive care unit of our hospital, 29 were excluded because they received other treatments or because of various underlying illnesses. Thus, eight patients were treated with midazolam and 10 with barbiturate coma therapy using thiamylal. Midazolam-treated patients were intubated only when necessary, whereas barbiturate coma therapy patients were routinely intubated. Continuous electroencephalography monitoring was utilized only for the barbiturate coma group. The titration goal for anesthesia was clinical termination of status epilepticus in the midazolam group and suppression or burst-suppression patterns on electroencephalography in the barbiturate coma group. Normothermia was maintained using blankets and neuromuscular blockade in the barbiturate coma group and using antipyretics in the midazolam group. Prognoses were measured at 1 month after onset; children were classified into poor and good outcome groups. Good outcome was achieved in all the barbiturate coma group patients and 50% of the midazolam group patients (P = 0.02, Fisher's exact test). Although the sample size was small and our study could not determine which protocol element is essential for the neurological outcome, the findings suggest that clinical seizure control using midazolam without continuous electroencephalography monitoring or targeted temperature management is insufficient in preventing neurological damage in children with convulsive refractory febrile status epilepticus. Copyright © 2014 Elsevier Inc. All rights reserved.
Myers, Kenneth A; McMahon, Jacinta M; Mandelstam, Simone A; Mackay, Mark T; Kalnins, Renate M; Leventer, Richard J; Scheffer, Ingrid E
Dravet syndrome (DS) is a well-recognized developmental and epileptic encephalopathy associated with SCN1A mutations and 15% mortality by 20 years. Although over half of cases succumb to sudden unexpected death in epilepsy, the cause of death in the remainder is poorly defined. We describe the clinical, radiologic, and pathologic characteristics of a cohort of children with DS and SCN1A mutations who developed fatal cerebral edema causing mass effect after fever-associated status epilepticus. Cases were identified from a review of children with DS enrolled in the Epilepsy Genetics Research Program at The University of Melbourne, Austin Health, who died after fever-associated status epilepticus. Five children were identified, all of whom presented with fever-associated convulsive status epilepticus, developed severe brain swelling, and died. All had de novo SCN1A mutations. Fever of 40°C or greater was measured in all cases. Signs of brainstem dysfunction, indicating cerebral herniation, were first noted 3 to 5 days after initial presentation in 4 patients, though were apparent as early as 24 hours in 1 case. When MRI was performed early in a patient's course, focal regions of cortical diffusion restriction were noted. Later MRI studies demonstrated diffuse cytotoxic edema, with severe cerebral herniation. Postmortem studies revealed diffuse brain edema and widespread neuronal damage. Laminar necrosis was seen in 1 case. Cerebral edema leading to fatal brain herniation is an important, previously unreported sequela of status epilepticus in children with DS. This potentially remediable complication may be a significant contributor to the early mortality of DS. Copyright © 2017 by the American Academy of Pediatrics.
Singhi, Pratibha; Saini, Arushi Gahlot; Sahu, Jitendra Kumar
Subacute sclerosing panencephalitis is a neurodegenerative disease secondary to measles infection that usually has a typical presentation with progressive myoclonia, cognitive decline, and periodic slow-wave complexes on electroencephalography. We report two pediatric cases who presented with periodic myoclonic jerks and cognitive decline. In both cases, the electroencephalogram showed continuous nonconvulsive status epilepticus activity. Both had elevated measles antibodies in cerebrospinal fluid and blood. Pediatricians need to be aware of this atypical presentation of subacute sclerosing panencephalitis. PMID:23094174
Tasker, Robert C; Goodkin, Howard P; Sánchez Fernández, Iván; Chapman, Kevin E; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Gaillard, William D; Glauser, Tracy A; Goldstein, Joshua; Helseth, Ashley R; Jackson, Michele C; Kapur, Kush; Mikati, Mohamad A; Peariso, Katrina; Wainwright, Mark S; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias
To describe pediatric patients with convulsive refractory status epilepticus in whom there is intention to use an IV anesthetic for seizure control. Two-year prospective observational study evaluating patients (age range, 1 mo to 21 yr) with refractory status epilepticus not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent. Nine pediatric hospitals in the United States. In a cohort of 111 patients with refractory status epilepticus (median age, 3.7 yr; 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment. The median (interquartile range) ICU length of stay was 10 (3-20) days. Up to four "cycles" of serial anesthetic therapy were used, and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9-34) hours for the first cycle and longer when a second cycle was required (30 [4-120] hr; p = 0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam nonresponders, transition to a second agent occurred after a median of 1 day. Most patients (94%) experienced seizure termination with these two therapies. Midazolam and pentobarbital remain the mainstay of continuous infusion therapy for refractory status epilepticus in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure, may be possible in a multicenter
Navalpotro-Gómez, Irene; Vivanco-Hidalgo, Rosa María; Cuadrado-Godia, Elisa; Medrano-Martorell, Santiago; Alameda-Quitllet, Francisco; Villalba-Martínez, Gloria; Roquer, Jaume
Idiopathic hypertrophic cranial pachymeningitis (IHCP) is an uncommon disease of unknown etiology characterized by thickening of the cerebral dura mater with possible associated inflammation. The most frequently described clinical symptoms include headache, cranial nerve palsy, and cerebellar dysfunction. Epilepsy and/or status epilepticus as main presentation is very uncommon. Two consecutive cases are presented of patients manifesting focal status epilepticus secondary to IHCP, with clinical, laboratory [blood test and cerebrospinal fluid (CSF) analysis], neuroradiologic [magnetic resonance imaging (MRI) at 3 Tesla and digital subtraction angiography (DSA)], and therapeutic data. One patient underwent meningeal biopsy; pathology findings are also included. Corticosteroid therapy resulted in clinical improvement in both cases, and neuroimaging showed decreased abnormal morphology, compared to initial findings. In the diagnostic approach to focal status epilepticus or epilepsy, IHCP must be considered a potential, although extremely infrequent, cause. Anti-inflammatory treatment is an effective addition to antiepileptic drug therapy in patients with IHCP. Copyright © 2016 Elsevier B.V. All rights reserved.
Power, Kjersti Nesheim; Gramstad, Arne; Gilhus, Nils Erik; Engelsen, Bernt A
Our objective was to study the semiology, aetiology, treatment and outcome of nonconvulsive status epilepticus (NCSE) in adults. All NCSE episodes in an unselected hospital cohort in the period 2004-2009 were identified, and the files reviewed. STESS (Status Epilepticus Severity Scale) was conducted retrospectively and correlated to outcome. Follow-up was undertaken after >2 years. 48 NCSEs in 39 patients, 22 men and 17 women, were found. Mean age was 63 years. 23/39 (59%) patients had established epilepsy. The underlying cause of NCSE was cerebrovascular disease in 17/39 (44%). 37/48 (77%) NCSEs were complex focal status epilepticus. 3/48 NCSEs (6.3%) lead to death, whereas 8.5% lead to severe sequelae. Cognitive sequelae were found after 14.9% of NCSEs. The outcome was worst in the group with no prior epilepsy (p=0.013). STESS had a negative predictive value of 96% (cut-off value of 3) for severe sequelae and death combined (p<0.002). NCSE has a potential for severe sequelae and represents an emergency in need of intensive treatment. The major determinant of outcome is the underlying cause. The outcome was worse in patients without epilepsy than in patients with epilepsy. STESS is of value in predicting outcome. Cognitive sequelae following NCSE can occur, but need further investigation with prospective, systematic studies. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Park, Hong-Kyun; Kim, Kyeong-Joon; Moon, Hye-Jin; Kim, Seon-Jeong; Yun, Chang-Ho; Park, Seong-Ho
Klüver-Bucy syndrome may result from affection of various location of brain. We report a case of Klüver-Bucy syndrome associated with isolated bilateral hippocampal atrophy without any abnormal lesion in other areas following status epilepticus. A 31-year-old man who had no significant medical history presented with status epilepticus after encephalitis of unknown etiology. He had been recovered from status epilepticus three weeks later, but afterwards he developed Klüver-Bucy syndrome: hyperphagia, hypersexuality, hypermetamorphosis, anterograde amnesia and dysosmia. Initial brain MRI showed T2 hyperintensity and swelling of isolated bilateral hippocampus, especially CA1 region without any abnormal lesion in other areas. One month later, follow-up brain MRI showed isolated bilateral hippocampal atrophy. This is a meaningful case report because this case differs from other reports of Klüver-Bucy syndrome in humans in that the anatomic abnormalities revealed by MRI were very selective. We report this case because this case is very educative for above reason. Moreover, this report would give us additional information of the relationship between human behavior and limbic system. PMID:24649454
Park, Hong-Kyun; Kim, Kyeong-Joon; Moon, Hye-Jin; Kim, Seon-Jeong; Yun, Chang-Ho; Park, Seong-Ho
Klüver-Bucy syndrome may result from affection of various location of brain. We report a case of Klüver-Bucy syndrome associated with isolated bilateral hippocampal atrophy without any abnormal lesion in other areas following status epilepticus. A 31-year-old man who had no significant medical history presented with status epilepticus after encephalitis of unknown etiology. He had been recovered from status epilepticus three weeks later, but afterwards he developed Klüver-Bucy syndrome: hyperphagia, hypersexuality, hypermetamorphosis, anterograde amnesia and dysosmia. Initial brain MRI showed T2 hyperintensity and swelling of isolated bilateral hippocampus, especially CA1 region without any abnormal lesion in other areas. One month later, follow-up brain MRI showed isolated bilateral hippocampal atrophy. This is a meaningful case report because this case differs from other reports of Klüver-Bucy syndrome in humans in that the anatomic abnormalities revealed by MRI were very selective. We report this case because this case is very educative for above reason. Moreover, this report would give us additional information of the relationship between human behavior and limbic system.
Waheed, Shahan; Sabeen, Amber; Ullah Khan, Nadeem
New onset refractory status epilepticus (NORSE) is a new entity in medical literature. It has different infectious and noninfectious etiologies showing a devastating impact onto the clinical outcome of patients. Therapy with anaesthetic and antiepileptic agents often fails to improve the condition, unless the primary cause is rectified. Here is presented the case of a young female with a history of depression who after a recent bereavement came to the Emergency Department of Aga Khan University Hospital with complaints of drowsiness that lasted for few hours. Though she had no history of organophosphate poisoning, her physical examination and further investigations were suggestive of the diagnosis. During her hospital stay, she developed refractory status epilepticus. Her seizures did not respond to standard antiepileptic and intravenous anesthetic agents and subsided only after intravenous infusion of atropine for a few days. Organophosphate poisoning is a very common presentation in the developing world and the associated status epilepticus poses a devastating problem for emergency physicians. In patients with suspected organophosphate poisoning with favoring clinical exam findings, the continuation of atropine intravenous infusion can be a safe option to abate seizures. PMID:25580311
Au, Cheuk C; Branco, Ricardo G; Tasker, Robert C
This systematic review of national or regional guidelines published in English aimed to better understand variance in pre-hospital and emergency department (ED) treatment of status epilepticus. Systematic search of national or regional guidelines (January 2000 to February 2017) contained within PubMed and Google Scholar databases, and article reference lists. The search keywords were status epilepticus, prolonged seizure, treatment, and guideline. 356 articles were retrieved and 13 were selected according to the inclusion criteria. In all six pre-hospital guidelines, the preferred route of medication administration was to use alternatives to the intravenous route: all recommended buccal and intranasal midazolam; three also recommended intramuscular midazolam, and five recommended using rectal diazepam. All 11 ED guidelines described three phases in therapy. Intravenous medication, by phase, was indicated as such: initial phase - ten/11 guidelines recommended lorazepam, and eight/11 recommended diazepam; second phase - most (ten/11) guidelines recommended phenytoin, but other options were phenobarbital (nine/11), valproic acid (six/11), and either fosphenytoin or levetiracetam (each four/11); third phase - four/11 guidelines included the choice of repeating second phase therapy, whereas the other guidelines recommended using a variety of intravenous anesthetic agents (thiopental, midazolam, propofol, and pentobarbital). All of the guidelines share a similar framework for management of status epilepticus. The choice in route of administration and drug type varied across guidelines. Hence, the adoption of a particular guideline should take account of local practice options in health service delivery. Copyright © 2017. Published by Elsevier Editora Ltda.
Caraballo, Roberto Horacio; Valenzuela, Gabriela Reyes; Armeno, Marisa; Fortini, Sebastian; Mestre, Graciela; Cresta, Araceli
We describe two patients with refractory myoclonic status epilepticus treated with the ketogenic diet. Between May 1, 2014 and January 1, 2015, two patients who met the diagnostic criteria for refractory myoclonic status epilepticus, seen at our department, were placed on the ketogenic diet and followed for a minimum of six months. One patient with myoclonic epilepsy of unknown aetiology had a 75-90% seizure reduction, and the other with progressive encephalopathy associated with myoclonic epilepsy had a 50% seizure reduction. Both patients retained good tolerability for the diet. At the last control, one patient had isolated myoclonias and EEG showed occasional generalized spike-and-polyspike waves; the patient is now successfully attending kindergarten. The quality of life of the second patient improved significantly. In both cases, the number of antiepileptic drugs was reduced. The ketogenic diet is an effective and well-tolerated treatment option for patients with refractory myoclonic status epilepticus and should be considered earlier in the course of treatment.
Rettenbeck, Maruja L; von Rüden, Eva-Lotta; Bienas, Silvia; Carlson, Regina; Stein, Veronika M; Tipold, Andrea; Potschka, Heidrun
Reactive oxygen species and inflammatory signaling have been identified as pivotal pathophysiological factors contributing to epileptogenesis. Considering the development of combined anti-inflammatory and antioxidant treatment strategies with antiepileptogenic potential, a characterization of the time course of microglial reactive oxygen species generation during epileptogenesis is of major interest. Thus, we isolated microglia cells and analyzed the generation of reactive oxygen species by flow cytometric analysis in an electrical rat post-status epilepticus model. Two days post status epilepticus, a large-sized cell cluster exhibited a pronounced response with excessive production of reactive oxygen species upon stimulation with phorbol-myristate-acetate. Neither in the latency phase nor in the chronic phase with spontaneous seizures a comparable cell population with induction of reactive oxygen species was identified. We were able to demonstrate in the electrical rat post-status-epilepticus model, that microglial ROS generation reaches a peak after the initial insult, is only marginally increased in the latency phase, and returns to control levels during the chronic epileptic phase. The data suggest that a combination of anti-inflammatory and radical scavenging approaches might only be beneficial during a short time window after an epileptogenic brain insult. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Ahmed, Yousef M.; Tarant, Nicki S.
Introduction. Classically, stress-induced cardiomyopathy (SIC), also known as takotsubo cardiomyopathy, displays the pathognomonic feature of reversible left ventricular apical ballooning without coronary artery stenosis following stressful event(s). Temporary reduction in ejection fraction (EF) resolves spontaneously. Variants of SIC exhibiting mid-ventricular regional wall motion abnormalities have been identified. Recent case series present SIC as a finding in association with sudden unexplained death in epilepsy (SUDEP). This case presents a patient who develops recurrence of nonapical cardiomyopathy secondary to status epilepticus. Case Report. Involving a postoperative, postmenopausal woman having two distinct episodes of status epilepticus (SE) preceding two incidents of SIC. Preoperative transthoracic echocardiogram (TTE) confirms the patient's baseline EF of 60% prior to the second event. Postoperatively, SE occurs, and the initial electrocardiogram exhibits T-wave inversions with subsequent elevation of troponin I. Postoperative TTE shows an EF of 30% with mid-ventricular wall akinesia restoring baseline EF rapidly. Conclusion. This case identifies the need to understand SIC and its diagnostic criteria, especially when cardiac catheterization is neither indicated nor available. Sudden cardiac death should be considered as a possible complication of refractory status epilepticus. The pathophysiology in SUDEP is currently unknown; yet a correlation between SUDEP and SIC is hypothesized to exist. PMID:28210509
Pizzi, Michael A; Kamireddi, Prasuna; Tatum, William O; Shih, Jerry J; Jackson, Daniel A; Freeman, William D
Nonconvulsive status epilepticus (NCSE) is a diagnosis that is often challenging and one that may progress to refractory NCSE. Ketamine is a noncompetitive N-methyl-d-aspartate antagonist that increasingly has been used to treat refractory status epilepticus. Current Neurocritical Care Society guidelines recommend intravenous (IV) ketamine infusion as an alternative treatment for refractory status epilepticus in adults. On the other hand, enteral ketamine use in NCSE has been reported in only 6 cases (1 adult and 5 pediatric) in the literature to date. A 33-year-old woman with a history of poorly controlled epilepsy presented with generalized tonic-clonic seizures, followed by recurrent focal seizures that evolved into NCSE. This immediately recurred within 24 h of a prior episode of NCSE that was treated with IV ketamine. Considering her previous response, she was started again on an IV ketamine infusion, which successfully terminated NCSE. This time, enteral ketamine was gradually introduced while weaning off the IV formulation. Treatment with enteral ketamine was continued for 6 months and then tapered off. There was no recurrence of NCSE or seizures and no adverse events noted during the course of treatment. This case supports the use of enteral ketamine as a potential adjunct to IV ketamine in the treatment of NCSE, especially in cases without coma. Introduction of enteral ketamine may reduce seizure recurrence, duration of stay in ICU, and morbidity associated with intubation.
Federman, Myke D; Kelly, Robert; Harrison, Rick E
The use of midazolam for the treatment of status epilepticus in children has generally been shown to be well tolerated and safe. Furthermore, encouraging efficacy has been observed when pediatric patients with status epilepticus have received continuous intravenous infusions of midazolam. A 9-year-old girl was treated with high-dose, continuous intravenous infusion of midazolam for the management of refractory status epilepticus. The patient developed a severe hyperchloremic, non-anion gap metabolic acidosis and resultant hemodynamic compromise, necessitating significant inotropic support and the initiation of a vasopressor infusion. We speculate that this complication was due to the preparation of parenteral midazolam with hydrochloric acid. The midazolam infusion was stopped, and, in less than 5 hours, the patient's metabolic acidosis resolved. The patient's inotropic and vasopressor infusions could only be weaned after discontinuing the use of high-dose midazolam. Although this complication was observed in only 1 pediatric patient with cortical dysplasia, caution and close clinical and laboratory surveillance should be exercised when administering continuous intravenous infusions of midazolam to pediatric patients.
Mastrangelo, Mario; Celato, Andrea
Status epilepticus (SE) is a life-threatening neurologic disorder comprising prolonged and unremitting crisis, and two or more series of seizures without complete intercritical recovery. We reviewed the literature through a Pubmed/Medline research using key words including status epilepticus, antiepileptic drugs and children, in order to revise and compare international/national protocols and to examine pediatric guidelines in SE management. Neurologic impairment and SE etiology seem to be the most independent risks for mortality. A deep semiologic evaluation is essential to addressing diagnostic work-up. Ematochemical parameters, plasma levels of antiepileptic drugs and clinically oriented toxic/metabolic screening should be mandatory for investigating both causes and effects of SE. Electroencephalography is clearly helpful to characterize focal from generalized SE and to distinguish epileptic events from pseudoseizures, and it is deal to find nonconvulsive SE. Neuroimaging techniques could detect epileptogenic lesions (such as cortical malformations, tumors, demyelinating disorders or strokes) but are common in practice to find negative or controversial results. Pharmacologic management can be essentially arranged in three stages: benzodiazepines for early SE (lasting less than 30 minutes), phenytoin/fosphenytoin, phenobarbital, valproate, levetiracetam or lacosamide for established SE (30-90 minutes), and anesthetics for refractory SE (more than 90 minutes). Status epilepticus is the most common neurologic emergency in childhood. A systematic diagnostic work-up and a three steps based therapeutic approach is required at this age.
Sánchez Fernández, Iván; Abend, Nicholas S; Agadi, Satish; An, Sookee; Arya, Ravindra; Carpenter, Jessica L; Chapman, Kevin E; Gaillard, William D; Glauser, Tracy A; Goldstein, David B; Goldstein, Joshua L; Goodkin, Howard P; Hahn, Cecil D; Heinzen, Erin L; Mikati, Mohamad A; Peariso, Katrina; Pestian, John P; Ream, Margie; Riviello, James J; Tasker, Robert C; Williams, Korwyn; Loddenkemper, Tobias
Status epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the 'pediatric Status Epilepticus Research Group' (pSERG). A literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network. The care of pediatric RCSE is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children. No comparative effectiveness trials have been performed in the pediatric population. Gaps in knowledge include risk factors for SE, biomarkers of SE and RCSE, second- and third-line treatment options, and long-term outcome. The care of children with RCSE is based on limited evidence. In order to address these knowledge gaps, the multicenter pSERG was established to facilitate prospective collection, analysis, and sharing of de-identified data and biological specimens from children with RCSE. These data will allow identification of treatment strategies associated with better outcomes and delineate evidence-based interventions to improve the care of children with SE. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
Topjian, Alexis A; Gutierrez-Colina, Ana M; Sanchez, Sarah M; Berg, Robert A; Friess, Stuart H; Dlugos, Dennis J; Abend, Nicholas S
Electrographic seizures and electrographic status epilepticus are common in critically ill children. We aimed to determine whether electrographic seizures and electrographic status epilepticus are associated with higher mortality or worse short-term neurologic outcome. Prospective observational study. PICU of a tertiary children's hospital. Non-neonatal children admitted to a PICU with acute encephalopathy underwent continuous electroencephalographic monitoring. Electroencephalographs were scored as 1) no seizures, 2) electrographic seizures, or 3) electrographic status epilepticus. Covariates included age, acute neurologic disorder category, prior neurodevelopmental status, sex, and electroencephalographic background category. Outcomes were mortality and worsening of pediatric cerebral performance category from preadmission to PICU discharge. Chi-square analysis, Fisher's exact test, and multivariable logistic regression were used to evaluate the associations between electrographic seizures or electrographic status epilepticus and mortality or short-term neurologic outcome, using odds ratios and 95% confidence intervals. None. Two hundred children underwent continuous electroencephalographic monitoring. Eighty-four (42%) had seizures, which were categorized as electrographic seizures in 41 (20.5%) and electrographic status epilepticus in 43 (21.5%). Thirty-six subjects (18%) died, and 88 subjects (44%) had pediatric cerebral performance category worsening. In multivariable analysis, electrographic status epilepticus was associated with an increased risk of mortality (odds ratio 5.1; 95% confidence interval 1.4, 18; p = 0.01) and pediatric cerebral performance category worsening (odds ratio 17.3; 95% confidence interval 3.7, 80; p < 0.001), whereas electrographic seizures were not associated with an increased risk of mortality (odds ratio 1.3; 95% confidence interval 0.3, 5.1; p = 0.74) or pediatric cerebral performance category worsening (odds ratio 1.2; 95
Giovannini, Giada; Monti, Giulia; Tondelli, Manuela; Marudi, Andrea; Valzania, Franco; Leitinger, Markus; Trinka, Eugen; Meletti, Stefano
Status epilepticus (SE) is a neurological emergency, characterized by high short-term morbidity and mortality. We evaluated and compared two scores that have been developed to evaluate status epilepticus prognosis: STESS (Status Epilepticus Severity Score) and EMSE (Epidemiology based Mortality score in Status Epilepticus). A prospective observational study was performed on consecutive patients with SE admitted between September 2013 and August 2015. Demographics, clinical variables, STESS-3 and -4, and EMSE-64 scores were calculated for each patient at baseline. SE drug response, 30-day mortality and morbidity were the outcomes measure. 162 episodes of SE were observed: 69% had a STESS ≥3; 34% had a STESS ≥4; 51% patients had an EMSE ≥64. The 30-days mortality was 31.5%: EMSE-64 showed greater negative predictive value (NPV) (97.5%), positive predictive value (PPV) (59.8%) and accuracy in the prediction of death than STESS-3 and STESS-4 (p<0.001). At 30 days, the clinical condition had deteriorated in 59% of the cases: EMSE-64 showed greater NPV (71.3%), PPV (87.8%) and accuracy than STESS-3 and STESS-4 (p<0.001) in the prediction of this outcome. In 23% of all cases, status epilepticus proved refractory to non-anaesthetic treatment. All three scales showed a high NPV (EMSE-64: 87.3%; STESS-4: 89.4%; STESS-3: 87.5%) but a low PPV (EMSE-64: 40.9%; STESS-4: 52.9%; STESS-3: 32%) for the prediction of refractoriness to first and second line drugs. This means that accuracy for the prediction of refractoriness was equally poor for all scales. EMSE-64 appears superior to STESS-3 and STESS-4 in the prediction of 30-days mortality and morbidity. All scales showed poor accuracy in the prediction of response to first and second line antiepileptic drugs. At present, there are no reliable scores capable of predicting treatment responsiveness. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Khongkhatithum, Chaiyos; Thampratankul, Lunliya; Wiwattanadittakul, Natrujee; Visudtibhan, Anannit
Intravenous levetiracetam is an option for treatment of status epilepticus (SE) and acute repetitive seizures (ARS). However, there have been relatively few studies with children and adolescents. Also, an appropriate dosage has yet to be determined. This study investigated the safety and the efficacy of levetiracetam for intravenous treatment of convulsive status epilepticus and acute repetitive seizures in children and adolescents. Retrospectively, the study reviewed the medical records of 19 male and 31 female patients under 18 years of age who had received intravenous levetiracetam treatment either for acute repetitive seizures or for convulsive status epilepticus. The patients were admitted between April 1st, 2010 and December 31st, 2011 to the Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Data were collected on underlying illnesses, etiology of seizures, indication for levetiracetam therapy, initial dosage, rate of infusion, untoward effects during infusion and emerged complications. Efficacy of treatment was defined as the termination of seizure within 30 min of completing levetiracetam infusion and no seizure recurrence within 6 h of initial treatment. The age range of the 50 patients was from one day to 18 years (mean 79.6 months). The analysis included 52 episodes of 34 acute repetitive seizures (63.4%) and 18 convulsive status epilepticus (34.6%). Infusion rates ranged from 2 to 66 mg/kg/min (mean 29.6). Cessation of seizure was obtained in 59.6% of 52 episodes. Patients with underlying drug resistant epilepsy did not respond to levetiracetam therapy as well as patients with other etiology of seizures. There were no adverse drug reactions or untoward effects observed during the therapy. Intravenous administration of levetiracetam is safe and effective for treatment of acute repetitive seizures and convulsive status epilepticus in children and adolescents. Failure of treatment may be related to
McClelland, A C; Gomes, W A; Shinnar, S; Hesdorffer, D C; Bagiella, E; Lewis, D V; Bello, J A; Chan, S; MacFall, J; Chen, M; Pellock, J M; Nordli, D R; Frank, L M; Moshé, S L; Shinnar, R C; Sun, S
The pathogenesis of febrile status epilepticus is poorly understood, but prior studies have suggested an association with temporal lobe abnormalities, including hippocampal malrotation. We used a quantitative morphometric method to assess the association between temporal lobe morphology and febrile status epilepticus. Brain MR imaging was performed in children presenting with febrile status epilepticus and control subjects as part of the Consequences of Prolonged Febrile Seizures in Childhood study. Medial temporal lobe morphologic parameters were measured manually, including the distance of the hippocampus from the midline, hippocampal height:width ratio, hippocampal angle, collateral sulcus angle, and width of the temporal horn. Temporal lobe morphologic parameters were correlated with the presence of visual hippocampal malrotation; the strongest association was with left temporal horn width (P < .001; adjusted OR, 10.59). Multiple morphologic parameters correlated with febrile status epilepticus, encompassing both the right and left sides. This association was statistically strongest in the right temporal lobe, whereas hippocampal malrotation was almost exclusively left-sided in this cohort. The association between temporal lobe measurements and febrile status epilepticus persisted when the analysis was restricted to cases with visually normal imaging findings without hippocampal malrotation or other visually apparent abnormalities. Several component morphologic features of hippocampal malrotation are independently associated with febrile status epilepticus, even when complete hippocampal malrotation is absent. Unexpectedly, this association predominantly involves the right temporal lobe. These findings suggest that a spectrum of bilateral temporal lobe anomalies are associated with febrile status epilepticus in children. Hippocampal malrotation may represent a visually apparent subset of this spectrum. © 2016 by American Journal of Neuroradiology.
Tsenov, G; Mares, P
Lithium-pilocarpine status epilepticus (SE) resulted in delayed changes of single cortical interhemisperic (transcallosal) responses in immature rats. Low-frequency stimulation inducing depression and/or potentiation was studied to analyze possible dynamic changes in cortical responses. Status was elicited in 12-day-old (SE12) or 25-day-old (SE25) rats. Control siblings received saline instead of pilocarpine. Interhemispheric responses were elicited by stimulation of the sensorimotor region of the cerebral cortex 3, 6, 9, 13, or 26 days after status. A series of 5 biphasic pulses with intensity equal to twofold threshold were used for stimulation. The interval between pulses was 100, 125, 160, 200 or 300 ms, eight responses were always averaged. Peak amplitude of the first positive, first negative and second positive waves was measured and responses to the second, third, fourth and fifth pulse were compared with the first one. Animals after status epilepticus as well as lithium-paraldehyde controls exhibit a frequency depression at nearly all the intervals studied. An outlined increase of responses in SE rats in comparison with the controls three days after SE stayed just below the level of statistical significance. In addition, animals in the SE12 group exhibited potentiation of responses at this interval after SE. With longer intervals after SE, the relation between SE and control animals changed twice resulting in a tendency to lower amplitude of responses in SE than in control rats 26 days after SE. Rats in the SE25 group exhibited higher responses than controls 13 days after status, but this difference was not present at the longest interval after SE. Low-frequency stimulation did not reveal increased cortical excitability as a long-lasting consequence of status epilepticus induced in immature rats. In addition, the outlined differences between SE and control rats changed with the time after SE.
Karlov, V A; Vlasov, P N; Gladov, B P; Kamelkova, E G
Authors assume that super-refractoriness is probably characterized by the specific pathophysiological mechanisms of status epilepticus development and can't be treated using standard treatment schemes. By the example of two clinical cases, we have analyzed the efficacy of complex treatment of super-refractory nonconvulsive and myoclonic status using intravenous valproate, central anesthetics (thiopental sodium, propofol), levetiracetam and cortexin. Preliminary results suggest that cortexin and levetiracetam as add-on to standard treatment may be vitally important drugs for the patients.
Doherty, J; Dingledine, R
Impaired GABAergic inhibition may contribute to the development of hyperexcitability in epilepsy. We used the pilocarpine model of epilepsy to demonstrate that regulation of excitatory synaptic drive onto GABAergic interneurons is impaired during epileptogenesis. Synaptic input from granule cells (GCs), perforant path, and CA3 inputs onto hilar border interneurons of the dentate gyrus were examined in rat hippocampal slices during the latent period (1-8 d) after induction of status epilepticus (SE). Short-term depression (STD) of GC inputs to interneurons induced by brief (500-800 msec), repetitive (5-20 Hz) stimulation, as well as paired-pulse depression at both GC and CA3 inputs to interneurons, were significantly (p < 0.05) enhanced in SE-experienced rats. In contrast, we found no significant differences between SE-experienced and age-matched control rats in the properties of minimal EPSCs evoked at low frequency (0.3 Hz). Consistent with reduced GABAergic inhibition onto granule cells, paired-pulse depression of perforant path-evoked granule cell population spikes was lost in SE-experienced rats. Enhanced STD was partially mediated by group II metabotropic glutamate receptors, because the selective antagonist, 2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid, attenuated STD in SE-experienced rats but had no effect on STD of GC inputs in the normal adult rat. The group II mGluR agonist, (2S',1R',2R',3R')-2-(2,3-dicarboxylcyclopropyl) glycine (1 micrometer), produced a greater depression of GC input to hilar border interneurons in SE-experienced rats than in controls. These results indicate that, in the SE-experienced rat, excitatory drive to hilar border inhibitory interneurons is weakened through a use-dependent mechanism involving group II metabotropic glutamate receptors.
Chiusolo, F; Diamanti, A; Bianchi, R; Fusco, L; Elia, M; Capriati, T; Vigevano, F; Picardo, S
Ketogenic diet (KD) has been used to treat refractory status epilepticus (RSE). KD is a high-fat, restricted-carbohydrate regimen that may be administered with different fat to protein and carbohydrate ratios (3:1 and 4:1 fat to protein and carbohydrate ratios). Other ketogenic regimens have a lower fat and higher protein and carbohydrate ratio to improve taste and thus compliance to treatment. We describe a case of RSE treated with intravenous KD in the Pediatric Intensive Care Unit (PICU). An 8-year-old boy was referred to the PICU because of continuous tonic-clonic and myoclonic generalized seizures despite several antiepileptic treatments. After admission he was intubated and treated with intravenous thiopental followed by ketamine. Seizures continued with frequent myoclonic jerks localized on the face and upper arms. EEG showed seizure activity with spikes on rhythmic continuous waves. Thus we decided to begin KD. The concomitant ileus contraindicated KD by the enteral route and we therefore began IV KD. The ketogenic regimen consisted of conventional intravenous fat emulsion, plus dextrose and amino-acid hyperalimentation in a 2:1 then 3:1 fat to protein and carbohydrate ratio. Exclusive IV ketogenic treatment, well tolerated, was maintained for 3 days; peristalsis then reappeared so KD was continued by the enteral route at 3:1 ratio. Finally, after 8 days and no seizure improvement, KD was deemed unsuccessful and was discontinued. Our experience indicates that IV KD may be considered as a temporary "bridge" towards enteral KD in patients with partial or total intestinal failure who need to start KD. It allows a prompt initiation of KD, when indicated for the treatment of severe diseases such as RSE. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Gorter, Jan A; van Vliet, Erwin A; Lopes da Silva, Fernando H
Experimental animal epilepsy research got a big boost since the discovery that daily mild and short (seconds) tetanic stimulations in selected brain regions led to seizures with increasing duration and severity. This model that was developed by Goddard (1967) became known as the kindling model for epileptogenesis and has become a widely used model for temporal lobe epilepsy with complex partial seizures. During the late ninety-eighties the number of publications related to electrical kindling reached its maximum. However, since the kindling procedure is rather labor intensive and animals only develop spontaneous seizures (epilepsy) after hundreds of stimulations, research has shifted toward models in which the animals exhibit spontaneous seizures after a relatively short latent period. This led to post-status epilepticus (SE) models in which animals experience SE after injection of pharmacological compounds (e.g. kainate or pilocarpine) or via electrical stimulation of (limbic) brain regions. These post-SE models are the most widely used models in epilepsy research today. However, not all aspects of mesial temporal lobe epilepsy (MTLE) are reproduced and the widespread brain damage is often a caricature of the situation in the patient. Therefore, there is a need for models that can better replicate the disease. Kindling, although already a classic model, can still offer valid clues in this context. In this paper, we review different aspects of the kindling model with emphasis on experiments in the rat. Next, we review characteristic properties of the post-SE models and compare the neuropathological, electrophysiological and molecular differences between kindling and post-SE epilepsy models. Finally, we shortly discuss the advantages and disadvantages of these models.
Reddy, Doodipala Samba; Kuruba, Ramkumar
This article describes current experimental models of status epilepticus (SE) and neuronal injury for use in the screening of new therapeutic agents. Epilepsy is a common neurological disorder characterized by recurrent unprovoked seizures. SE is an emergency condition associated with continuous seizures lasting more than 30 min. It causes significant mortality and morbidity. SE can cause devastating damage to the brain leading to cognitive impairment and increased risk of epilepsy. Benzodiazepines are the first-line drugs for the treatment of SE, however, many people exhibit partial or complete resistance due to a breakdown of GABA inhibition. Therefore, new drugs with neuroprotective effects against the SE-induced neuronal injury and degeneration are desirable. Animal models are used to study the pathophysiology of SE and for the discovery of newer anticonvulsants. In SE paradigms, seizures are induced in rodents by chemical agents or by electrical stimulation of brain structures. Electrical stimulation includes perforant path and self-sustaining stimulation models. Pharmacological models include kainic acid, pilocarpine, flurothyl, organophosphates and other convulsants that induce SE in rodents. Neuronal injury occurs within the initial SE episode, and animals exhibit cognitive dysfunction and spontaneous seizures several weeks after this precipitating event. Current SE models have potential applications but have some limitations. In general, the experimental SE model should be analogous to the human seizure state and it should share very similar neuropathological mechanisms. The pilocarpine and diisopropylfluorophosphate models are associated with prolonged, diazepam-insensitive seizures and neurodegeneration and therefore represent paradigms of refractory SE. Novel mechanism-based or clinically relevant models are essential to identify new therapies for SE and neuroprotective interventions. PMID:24013377
Wang, Jin; Liu, Yuan; Li, Xiao-Hui; Zeng, Xiang-Chang; Li, Jian; Zhou, Jun; Xiao, Bo; Hu, Kai
Status epilepticus, the most severe form of epilepsy, is characterized by progressive functional and structural damage in the hippocampus, ultimately leading to the development and clinical appearance of spontaneous, recurrent seizures. Although the pathogenesis underlying epileptogenesis processes remains unclear, a substantial body of evidence has shown that status epilepticus acts as an important initial factor in triggering epileptogenesis. Notably, besides classical cell death mechanisms such as apoptosis and necrosis, 2 novel regulators of cell fate known as necroptosis and autophagy, are demonstrated to be involved in neuronal damage in various neurodegenerative and neuropsychiatric disorders. However, whether necroptosis and autophagy play a role in post-status-epilepticus rat hippocampus and other epilepsy mechanisms deserves further research effort. In addition, research is needed to determine whether compounds from traditional Chinese herbs possess antiepileptic effects through the modulation of necroptosis and autophagy. In this study, we found that curcumin, a polyphenolic phytochemical extracted from the Curcuma longa plant, protects neuronal cells against status-epilepticus-induced hippocampal neuronal damage in the lithium-pilocarpine-induced status epilepticus rat model through induction of autophagy and inhibition of necroptosis.
Kirkpatrick, McNeill P; Clarke, Charles D; Sonmezturk, Hasan H; Abou-Khalil, Bassel
Anti-NMDA receptor antibody encephalitis is a limbic encephalitis with psychiatric manifestations, abnormal movements, coma, and seizures. The coma and abnormal movements are not typically attributed to seizure activity, and slow activity is the most common EEG finding. We report drug-resistant nonconvulsive status epilepticus as the basis for coma in a 19-year-old woman with anti-NMDA receptor antibodies and a mediastinal teratoma. The EEG showed generalized rhythmic delta activity, with evolution in morphology, frequency, and field typical of nonconvulsive status epilepticus. The status was refractory to antiepileptic drugs, repeated drug-induced coma, resection of the tumor, intravenous steroids, rituximab, and plasmapheresis. She awoke after the addition of felbamate, and the rhythmic delta activity ceased. The rhythmic delta activity described with coma in anti-NMDA receptor antibody encephalitis may represent a pattern of status epilepticus in some patients. Felbamate, which has NMDA receptor antagonist activity, should be studied as a therapeutic agent in this condition.
Chamberlain, James M.; Capparelli, Edmund V.; Brown, Kathleen M.; Vance, Cheryl W.; Lillis, Kathleen; Mahajan, Prashant; Lichenstein, Richard; Stanley, Rachel M.; Davis, Colleen O.; Gordon, Stephen; Baren, Jill M.; van den Anker, John N.
Objective[mh2] To evaluate the single dose pharmacokinetics of an intravenous dose of lorazepam in pediatric patients treated for status epilepticus (SE) or with a history of SE. Study design Ten hospitals in the Pediatric Emergency Care Applied Research Network (PECARN) enlisted patients 3 months to 17 years with convulsive SE (STATUS) or for a traditional PK study (ELECTIVE). Sparse sampling was used for STATUS and intensive sampling for ELECTIVE. Noncompartmental analyses were performed on ELECTIVE, and served to nest compartmental population PK analysis for both cohorts. Results 48 STATUS and 15 ELECTIVE patients were enrolled. Median age was 7 years, 2 months. The population PK parameters were: clearance 1.2 mL/min/kg, half-life 16.8 hours, volume of distribution 1.5 L/kg. Based on the PK model, a 0.1 mg/kg dose is expected to achieve concentrations of approximately 100 ng/mL and maintain concentrations above 30–50 ng/mL for 6–12 hours. A second dose of 0.05 mg/kg would achieve desired therapeutic serum levels for approximately 12 hours without excessive sedation. Age-dependent dosing is not necessary beyond using a maximum initial dose of 4 mg. Conclusions Lorazepam PK in convulsive status epilepticus is similar to previous PK measured in pediatric patients with cancer, except for longer half-life and similar to adult PK parameters except for increased clearance. PMID:22050870
Pearce, Patrice S; Wu, Yijen; Rapuano, Amedeo; Kelly, Kevin M; de Lanerolle, Nihal; Pan, Jullie W
In vivo studies of epilepsy typically use prolonged status epilepticus to generate recurrent seizures. However, reports on variable status duration have found discrete differences in injury after 40-50 min of seizures, suggesting a pathophysiologic sensitivity to seizure duration. In this report we take a multivariate cluster analysis to study a short duration status epilepticus model using in vivo 7T magnetic resonance spectroscopy (MRS) and histologic evaluation. The Hellier Dudek model was applied with 45 min of status epilepticus after which the animals were imaged twice, at 3 days and 3 weeks post-status epilepticus. Single voxel point resolved spectroscopy (PRESS) MRS was used to acquire data from the dentate gyrus and CA3 region of the hippocampus, assessing metabolite ratios to total creatine (tCr). In a subset of animals after the second imaging study, brains were analyzed histologically by Nissl staining. A hierarchical cluster analysis performed on the 3-day data from 21 kainate-treated animals (dentate gyrus voxel) segregated into two clusters, denoted by KM (more injured, n = 6) and KL (less injured, n = 15). Although there was no difference in kainate dosing or seizure count between them, the metabolic pattern of injury was different. The KM group displayed the largest significant changes in neuronal and glial parameters; the KL group displayed milder but significant changes. At 3 weeks, the KL group returned to normal compared to controls, whereas the KM group persisted with depressed N-acetyl aspartate (NAA)/tCr, glutamate/tCr, and increased inositol/tCr and glutamine/tCr. The classification was also consistent with subsequent histologic patterns at 3 weeks. Although a short status period might be expected to generate a continuous distribution of metabolic injury, these data show that the short Hellier Dudek model appears to generate two levels of injury. The changes seen in segregated groups persisted into 3 weeks, and can be interpreted according
Cardoso, Ingrid; Acevedo, Keryma; Hernández, Marta; Santin, Julia; Moya, Pedro; Godoy, Jaime; Castillo, Andrés; Soto, Pilar; Mesa, Tomás
Patients with refractory status epilepticus (RSE) have high morbidity and mortality rates, are hospitalised for longer periods of time, suffer greater neurological damage and progress to symptomatic epilepsy. Continuous electroencephalogram (cEEG) monitoring is a valuable aid in the early detection of RSE, especially in the case of non-convulsive status epilepticus (NCSE). In this study we describe the clinical characteristics, treatment and use of cEEG in paediatric patients with RSE. A retrospective study was conducted at the Hospital Clinico de la Pontificia Universidad Catolica de Chile between November 2005 and March 2011 in patients aged between 1 month and 15 years diagnosed with RSE and cEEG. Demographic characteristics, baseline and final conditions, and therapy were recorded. A total of 15 patients, 12 of whom were males, with a mean age of 4 years (1.5 months-13 years) were identified. Eight patients had a history of epilepsy. The most frequent aetiologies were progressive symptomatic and acute symptomatic. Convulsive epileptic status (CSE) was present in 11 patients and NCSE in the other four. During the cEEG, six of the 11 patients with CSE later progressed to NCSE. The mean amount of time with RSE was 10.2 days. Of the 15 patients, 13 responded to anticonvulsive drugs and the main secondary complications were respiratory depression and hypotension. Patients with CSE tended to evolve in a more torpid manner than patients with NCSE. On discharge from hospital, 13 patients (86.6%) presented new neurological deficit or difficult-to-manage epilepsy, one still had RSE and one died (6%). The aggregate neurological morbidity and mortality rates of RSE were high. The use of cEEG monitoring should be considered for use in the management of such cases of status epilepticus.
Momen, Ali Akbar; Azizi Malamiri, Reza; Nikkhah, Ali; Jafari, Maryam; Fayezi, Abbas; Riahi, Kourosh; Maraghi, Elham
The aim of this study was to evaluate the efficacy and safety of intramuscular midazolam in controlling convulsive status epilepticus in children, by comparing it with rectal diazepam. In this randomized trial, 100 children (50 in each group) with convulsive status epilepticus aged 1 month to 16 years were enrolled and randomly assigned into two groups to receive either 0.3 mg/kg intramuscular midazolam or 0.5 mg/kg rectal diazepam. Main outcome measure was stopping of all motor activity after drug administration. Another measures were times between patient's arrival to emergency department till drug administration, between drug administration to seizure cessation, and between patient's arrival to seizure cessation. Both medication were effective for seizure control and no significant difference was found between successful treatments after administering the medication (P = 0.061). In the midazolam group, in 96% (48/50) of cases treatment was successful and in the diazepam group, in 94% (47/50) of cases treatment was successful. Time from arrival to administering the medication was significantly shorter in midazolam group (P = 0.017). The majority of seizures in midazolam group were stopped in less than 66 s (median) compared to 130 s (median) for diazepam group, (P < 0.001). No serious adverse effects were seen in both groups. IM midazolam is not superior but may be at least as effective as rectal diazepam for controlling of status epilepticus in children. Midazolam via IM route could be one of the choices in children with convulsive status seizures who have difficult IV access. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Byun, Jung-Ick; Chu, Kon; Sunwoo, Jun-Sang; Moon, Jangsup; Kim, Tae-Joon; Lim, Jung-Ah; Jun, Jin-Sun; Lee, Han Sang; Lee, Woo-Jin; Lee, Doo Young; Jeon, Daejong; Lee, Soon-Tae; Jung, Keun-Hwa; Jung, Ki-Young; Lee, Sang Kun
To evaluate the efficacy and safety of mega-dose phenobarbital (MDPB; enteral or parenteral phenobarbital >10 mg/kg/day) for treating super-refractory status epilepticus (SRSE; continuous or recurrent status epilepticus for ≥24 hours after the onset of continuous anaesthetic treatment) in adult patients. Adult patients with SRSE who were treated with MDPB in our institution from March 2005 to September 2014 were reviewed. We collected data on basic demographics, clinical features, functional status, anticonvulsant treatment, and possible adverse events. SRSE outcome was divided into six categories: successful therapy, initial failure, breakthrough seizures, withdrawal seizures, intolerable side effects, and death during treatment. Ten adult patients with SRSE received MDPB. Median age at seizure onset was 38 years (range: 18-59), and half were male. All patients had no history of seizures and had symptoms suggestive of viral encephalitis. Median duration of status epilepticus was 17.5 days (range: 6-60) and anaesthetics were used for a median of 14.0 days (range: 2-54) before MDPB. Successful control of SRSE was achieved in half of the patients, however, only one of ten patients was able to fully recover at discharge. Median duration of the MDPB was 45.5 days and the maximum serum phenobarbital level reached a median of 151.5 μg/ml. Patients with successful MDPB therapy had normal brain imaging (80% vs. 0%; p=0.048) and better functional outcome at discharge and after three months of follow-up. Infection was the most critical complication, along with cardiorespiratory depression. MDPB is a therapeutic option for control of SRSE when other choices are exhausted.
Savitskaia, O N; Karlov, V A; Gleĭzer, M A; Pmotskaia, E E
A unique observation of an epileptic female examined in detail in a neurological clinic is presented. The patient was later hospitalized 3 times for disturbances of consciousness and extrapyramid disorders characterized by acute onset. An encephalographic examination carried out during such a state showed an epileptic status of atypic absence. The development of the Parkinsonian syndrome is regarded as a proof of the role of the caudate nucleus in the genesis of the petit mal epileptic status.
Marziali, Simone; Di Giuliano, Francesca; Picchi, Eliseo; Natoli, Silvia; Leonardis, Carlo; Leonardis, Francesca; Garaci, Francesco; Floris, Roberto
The presentation of carbon monoxide poisoning is non-specific and highly variable. Hyperbaric oxygen therapy is used for the treatment of this condition. Various reports show the occurrence of self-limiting seizures after carbon monoxide poisoning and as a consequence of hyperbaric oxygen therapy. Contrary to the seizures, status epilepticus has been rarely observed in these conditions. The exact pathophysiology underlying seizures and status epilepticus associated with carbon monoxide poisoning and hyperbaric oxygen therapy is not really clear, and some elements appear to be common to both conditions. We describe a case of non-convulsive status epilepticus in a patient with carbon monoxide poisoning treated with hyperbaric oxygen therapy. The mechanism, MRI findings and implications are discussed.
Kantanen, Anne-Mari; Reinikainen, Matti; Parviainen, Ilkka; Ruokonen, Esko; Ala-Peijari, Marika; Bäcklund, Tom; Koskenkari, Juha; Laitio, Ruut; Kälviäinen, Reetta
Super-refractory status epilepticus (SRSE) is defined as status epilepticus (SE) that continues or recurs 24h or more after the onset of anesthetic therapy. We defined the incidence and outcome of SRSE in adults in Finland. We analyzed retrospectively the Finnish Intensive Care Consortium database in order to identify adult patients with SRSE treated in ICUs in Finland during a three-year period (2010-2012). The database consists of admissions to all 20 Finnish hospitals treating refractory SE (RSE) with general anesthesia in the intensive care unit (ICU). We included consecutive adult (16 years or older) patients with RSE and identified those who had SRSE. Patients with postanoxic etiologies were excluded. All five university hospitals and 10/15 of the central hospitals participated. The adult referral population of the study hospitals is 3.9 million, representing 91% of the total adult population of Finland. We identified 395 patients with ICU-treated RSE, 87 (22%) of whom were classified as having SRSE. This corresponds to an annual incidence of SRSE of 0.7/100,000 (95% confidence interval [CI]: 0.6-0.9). The one-year mortality rates were 36% (95% CI: 26-46%) for patients with SRSE and 22% (95% CI: 17-27%) for patients with RSE. Mortality was highest (63%) in patients with SRSE aged over 75 years. Approximately 20% of patients with RSE treated in Finnish ICUs progressed to having SRSE. The incidence of SRSE, 0.7/100,000, is about 5-10% of the incidence of SE. The mortality of patients with SRSE, 36%, was comparable to earlier studies and twofold higher than the mortality of patients with RSE. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.
Delaj, L; Novy, J; Ryvlin, P; Marchi, N A; Rossetti, A O
While status epilepticus (SE) persisting after two antiseizure agents is called refractory (RSE), super-refractory status epilepticus (SRSE) defines SE continuing after general anaesthesia. Its prevalence and related clinical profiles have received limited attention, and most studies were restricted to intensive care facilities. We therefore aimed at describing RSE and SRSE frequencies and identifying associated clinical variables. Between 2006 and 2015, consecutive adult SE episodes were prospectively recorded in a registry. Occurrence of RSE and SRSE and their relationship to clinical variables of interest, including outcome, were analysed. Of 804 SE episodes, 268 (33.3%) were RSE and 33 (4%) SRSE. Coma induction for SE treatment occurred in 79 (9.8%) episodes. Severe consciousness impairment (OR 1.67; 95% CI 1.24-2.46; P = 0.001), increasing age (OR 1.01, 95% CI 1.01-1.02), and lack of remote symptomatic SE aetiology (OR 0.48; 95% CI 0.32-0.72) were independently associated with RSE, while severe consciousness impairment (OR 4.26; 95% CI 1.44-12.60) and younger age (OR 0.96; 95% CI 0.95-0.99) correlated with SRSE; however, most SRSE episodes were not predicted by these variables. Mortality was 15.5% overall, higher in RSE (24.5%) and SRSE (37.9%) than in non-refractory SE (9.8%) (P < 0.001). Super-refractory status epilepticus appears clearly less prevalent in this cohort than previously reported, probably as it is not restricted to intensive care unit. SRSE emerges in younger patients with marked consciousness impairment, pointing to the underlying severe clinical background, but these variables do not predict most SRSE developments. There is currently a knowledge gap for prediction of SRSE occurrence that needs to be filled. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Sánchez Fernández, Iván; Vendrame, Martina; Kapur, Kush; Klehm, Jacqueline; Uysal, Serife; Gedik, Mustafa; An, Sookee; Jillella, Dinesh; Zelener, Jacqueline; Syed, Sana; Gooty, Vasu; Rotenberg, Alexander; Loddenkemper, Tobias
The most common thresholds for considering prolonged seizures as status epilepticus (SE) are 5 and 30 min. It is unknown whether these different thresholds (5 or 30 min) identify patient populations with different electroclinical characteristics. We compared the characteristics of patients with SE lasting 5-29 min (SE5-29) with those with SE lasting ≥30 min (SE≥30). Inclusion criteria were the following: 1) 1 month to 21 years of age at the time of SE, 2) convulsive seizures, and 3) seizure duration ≥5 min. Exclusion criteria were the following: 1) exclusively neonatal seizures, 2) psychogenic nonepileptic seizures, or 3) incomplete information about seizure duration. Four hundred forty-five patients (50.1% male) with a median (p25-p75) age at SE of 5.5 (2.8-10.5) years were enrolled. Status epilepticus lasted for 5-29 min in 296 (66.5%) of subjects and for ≥30 min in 149 (33.5%). Patients with SE≥30 were younger than the patients with SE5-29 at the time of seizure onset (median: 1 versus 2.1 years, p=0.0007). Status epilepticus as the first seizure presentation was more frequent in patients with SE≥30 (24.2% versus 12.2%, p=0.002). There was a tendency towards a higher rate of abnormalities in the magnetic resonance imaging at baseline in patients with SE≥30 (70.5% versus 57.1%, p=0.061). Differences were not detected in seizure frequency, seizure types, presence of developmental delay, and electroencephalogram abnormalities at baseline. In the pediatric population, SE thresholds of either 5 or 30 min identify groups of patients with very similar electroclinical characteristics, which may influence future definitions of pediatric SE. Copyright © 2014 Elsevier Inc. All rights reserved.
Bhalla, Ashish; Das, Biplab; Som, Rimi; Prabhakar, Sandeep; Kharbanda, Parampreet S.
Introduction: Status epilepticus (SE) is a medical emergency. Aim of this study was to examine the etiology and outcome of adult patients in status epilepticus presenting to our center. Patients and Methods: A prospective study was conducted from January 2009 to December 2010. Newly diagnosed patients as well as known case of seizure disorder presenting with status epilepticus were included. Detailed history, clinical examination, baseline investigation, neuroimaging electroencephalogram findings were recorded. Patients were treated using a standard protocol and were followed-up for 2 weeks after discharge. Quantification of precipitating factors was done using proportion, mean and standard deviation. Results: 80 consecutive patients were studied. Mean age was 38.43 ± 16.56 years (range 13 to 78 years). Male to female ratio was 4:1. 57.5% were known cases of seizure disorders. Generalized tonic-clonic seizure was commonest presentation in 91.30%. Majority (97.5%) had convulsive SE. Poor drug compliance was found to be the commonest precipitant (50% patients), followed by central nervous system infection (20% patients. Alcohol intake contributed in 12.5% cases, whereas, precipitating factor couldn't be traced in 7.5% patients'. In 55% patients, SE was controlled with no recurrence or complication and in 25% there was recurrence after control of SE. 15% patients ended up with persistent sequel (cognitive and psychosomatic dysfunction, neurological deficit etc.) lasting for 2 weeks or more. The mortality was 5%. Conclusion: Poor compliance with drugs (in established cases of seizure disorders) and central nervous systems infections/structural lesions (in new onset cases) were commonest causes of SE in our study group. Conventional first line antiepileptics were able to control seizures in only 55% patients. PMID:24550623
Kang, Bong Su; Jung, Keun-Hwa; Shin, Jeong-Won; Moon, Jang Sup; Byun, Jung-Ick; Lim, Jung-Ah; Moon, Hye Jin; Kim, Young-Soo; Lee, Soon-Tae; Chu, Kon; Lee, Sang Kun
General anesthetic-induced coma therapy has been recommended for the treatment of refractory status epilepticus (RSE). However, the influence of electroencephalographic (EEG) burst suppression (BS) on outcomes still remains unclear. This study investigated the impact of intravenous anesthetic-induced BS on the prognosis of RSE using a retrospective analysis of all consecutive adult patients who received intravenous anesthetic treatment for RSE at the Seoul National University Hospital between January 2006 and June 2011. Twenty-two of the 111 episodes of RSE were enrolled in this study. Of the 22 RSE patients, 12 (54.5%) were women and 18 (81.4%) exhibited generalized convulsive status epilepticus. Sixteen patients (72.7%) were classified as having acute symptomatic etiology, including three patients with anoxic encephalopathy, and others with remote symptomatic etiology. Only two patients (9.1%) had a favorable Status Epilepticus Severity Score (0-2) at admission. All patients received midazolam (MDZ) as a primary intravenous anesthetic drug for RSE treatment; three (13.6%) received MDZ and propofol, and one (4.5%) received MDZ and pentobarbital. The rates of mortality and poor outcome at discharge were 13.6% (n=3) and 54.5% (n=12), respectively. While BS was achieved in six (27.5%) patients, it was not associated with mortality or poor outcome. Induced BS was associated with prolonged hospital stay in subgroup analysis when excluding anoxic encephalopathy. Our results suggest that induction of BS for treating RSE did not affect mortality or outcome at discharge and may lead to an increased length of hospital stay. Copyright © 2014 Elsevier Ltd. All rights reserved.
Zahr, Natalie M.; Fasano Crawford, Elena L.; Hsu, Oliver; Vinco, Shara; Mayer, Dirk; Rohlfing, Torsten; Sullivan, Edith V.; Pfefferbaum, Adolf
Neurophysiological, biochemical, and anatomical evidence implicates glutamatergic mechanisms in epileptic seizures. Until recently, however, longitudinal characterization of in vivo glutamate dynamics was not possible. Here, we present data using in vivo magnetic resonance spectroscopy (MRS) optimized for the detection of glutamate to identify changes that evolve following kainic acid (KA)-induced status epilepticus. Wild-type male Wistar rats underwent whole brain MR imaging and single voxel MRS on a clinical 3T scanner equipped with a high-strength insert gradient coil. Scanning took place before and then 3 days, 28 – 32 days, and 42 – 50 days after induction of status epilepticus. Analyses compared 5 seizure (Sz), 5 no-seizure (NoSz; received KA but did not exhibit seizures), and 6 control (Con) animals. This longitudinal study demonstrated reduced glutamate levels in vivo in the dorsal hippocampus 3 days and 1 month following status epilepticus in Sz animals compared with Con animals. Additionally, previous results were replicated: in the Sz group, computed T2 was higher in the ventral hippocampus and limbic cortex 3 days after seizure activity compared with baseline but resolved in both regions at the 1 month scan, suggesting a transient edema. Three days following seizure activity, N-acetylaspartate (NAA) declined and lactate increased in the dorsal hippocampus of the Sz group compared with the Con and NoSz group; both metabolites approached baseline levels by the third scan. Taken together, these results support the conclusion that seizure activity following KA infusion causes loss of glutamatergic neurons. PMID:19715683
Nishiyama, Masahiro; Nagase, Hiroaki; Tanaka, Tsukasa; Fujita, Kyoko; Maruyama, Azusa; Toyoshima, Daisaku; Nakagawa, Taku; Taniguchi-Ikeda, Mariko; Morioka, Ichiro; Morisada, Naoya; Takada, Satoshi; Iijima, Kazumoto
Convulsive status epilepticus with fever is common and may be related to neurological sequela in children. However, there are limited data on the demographics and risk factors of this phenomenon. Thus, we aimed to describe the demographics and risk factors of neurological sequela among children with convulsive status epilepticus with fever. We reviewed convulsive status epilepticus with fever cases in the pediatric intensive care unit at Kobe Children's Hospital between 2002 and 2013. We included patients with intrinsic neurological disease, and excluded those with obvious central nervous system infection. Cases of neurological worsening were categorized as poor outcome using the pediatric cerebral performance category scale. Possible risk factors for poor outcome included age, sex, neurological medical history, seizure duration, body temperature, and level of consciousness. A total of 253 patients (128 males), aged 1 month to 15 years (mean 45 ± 40 months), were enrolled. Three patients (1.2%) died during hospitalization, and 32 (12.6%) patients had a poor outcome. A univariate analysis identified male sex, absence of epilepsy history, body temperature above 40°C on admission, seizure duration longer than 120 minutes, impaired consciousness at 12 hours after onset, and presence of nonconvulsive seizure as potential predictors of poor outcome. A multivariate analysis, revealed that an absence of epilepsy history (odds ratio = 11.18), body temperature above 40°C on admission (odds ratio = 3.39), or impaired consciousness at 12 hours after onset (odds ratio = 41.85) was associated with poor outcome. Our study indicated that absence of epilepsy history, high temperature, and/or prolonged impaired consciousness were associated with brain injury. Copyright © 2015 Elsevier Inc. All rights reserved.
557-560. 14 Mailliet F, Galloux P and Poisson D. Comparative effects of melatonin , zolpidem and diazepam on sleep, body temperature, blood pressure...Levin ED. Long-term neuroprotection by benzodiazepine full versus partial agonists after transient cerebral ischemia in the gerbil [corrected]. J
Cobo, Nicole H; Sankar, Raman; Murata, Kristina K; Sewak, Sarika L; Kezele, Michele A; Matsumoto, Joyce H
Refractory status epilepticus carries significant morbidity and mortality. Recent reports have promoted the use of the ketogenic diet as an effective treatment for refractory status epilepticus. We describe our recent experience with instituting the ketogenic diet for 4 critically ill children in refractory status epilepticus, ranging in age from 9 weeks to 13.5 years after failure of traditional treatment. The ketogenic diet allowed these patients to be weaned off continuous infusions of anesthetics without recurrence of status epilepticus, though delayed ketosis and persistently elevated glucose measurements posed special challenges to effective initiation, and none experienced complete seizure cessation. The ease of sustaining myocardial function with fatty acid energy substrates compares favorably over the myocardial toxicity posed by anesthetic doses of barbiturates and contributes to the safety profile of the ketogenic diet. The ketogenic diet can be implemented successfully and safely for the treatment of refractory status epilepticus in pediatric patients.
Leitinger, M; Beniczky, S; Rohracher, A; Gardella, E; Kalss, G; Qerama, E; Höfler, J; Hess Lindberg-Larsen, A; Kuchukhidze, G; Dobesberger, J; Langthaler, P B; Trinka, E
Salzburg Consensus Criteria for diagnosis of Non-Convulsive Status Epilepticus (SCNC) were proposed at the 4th London-Innsbruck Colloquium on status epilepticus in Salzburg (2013). We retrospectively analyzed the EEGs of 50 consecutive nonhypoxic patients with diagnoses of nonconvulsive status epilepticus (NCSE) at discharge and 50 consecutive controls with abnormal EEGs in a large university hospital in Austria. We implemented the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology, 2012 version (ACNS criteria) to increase the test performance of SCNC. In patients without preexisting epileptic encephalopathy, the following criteria were applied: (1) more than 25 epileptiform discharges (ED) per 10-second epoch, i.e., >2.5/s and (2) patients with EDs ≤ 2.5/s or rhythmic delta/theta activity (RDT) exceeding 0.5/s AND at least one of the additional criteria: (2a) clinical and EEG improvements from antiepileptic drugs (AEDs), (2b) subtle clinical phenomena, or (2c) typical spatiotemporal evolution. In case of fluctuation without evolution or EEG improvement without clinical improvement, "possible NCSE" was diagnosed. For identification of RDT, the following criteria were compared: (test condition A) continuous delta-theta activity without further rules, (B) ACNS criterion for rhythmic delta activity (RDA), and (C) ACNS criteria for RDA and fluctuation. False positive rate in controls dropped from 28% (condition A) to 2% (B) (p = 0.00039) and finally to 0% (C) (p = 0.000042). Application of test condition C in the group with NCSE gives one false negative (2%). Various EEG patterns were found in patients with NCSE: (1) 8.2%, (2a) 2%, (2b) 12.2%, and (2c) 32.7%. Possible NCSE was diagnosed based on fluctuations in 57.1% and EEG improvement without clinical improvement in 14.2%. The modified SCNC with refined definitions including the ACNS terminology leads to clinically relevant and statistically significant reduction of false
Dimitriadis, Konstantinos; Pfefferkorn, Thomas; Noachtar, Soheyl
Depression as well as fear, joy and anger have been described as the semiological features of focal epileptic seizures. When emotions present as the sole symptoms of epileptic seizures, they may easily be misdiagnosed as a psychiatric disorder. We describe a patient with affective focal status epilepticus, secondary to limbic encephalitis, in which depression was the only clinical manifestation. Through EEG correlates the epileptic nature of depression could be proven. Furthermore, we discuss the association between epilepsy and depression, as well as the link between ictal depression and suicidal rates. PMID:24827645
Lapenta, Leonardo; Frisullo, Giovanni; Vollono, Catello; Brunetti, Valerio; Giannantoni, Nadia Mariagrazia; Sandroni, Claudio; Di Lella, Giuseppe; Della Marca, Giacomo
Super-refractory status epilepticus (SE; ie, SE continuing or recurring despite 24 hours of general anesthesia) is a severe condition with high percentage of mortality and morbidity. Usually, this condition occurs because of serious brain damage; nevertheless, some patients develop super-refractory SE without identifiable etiology. Although not uncommonly encountered in neurointensive care, scientific data on this condition are still lacking in terms of treatment and prognosis. Herein, we report a case of super-refractory SE with recovery after 50 days, despite electroencephalographic (EEG) and magnetic resonance imaging (MRI) signs traditionally related to poor prognosis. A review of the literature on super-refractory SE is also presented.
Olafsson, E; Magnusson, T
Non-convulsive status epilepticus is a rare form of epilepsy. The predominant clinical feature is prolonged loss of consciousness without prominent motor features. The diagnosis is often difficult because of the non-specific nature of the symptoms and this diagnostic possibility has to be born in mind when patients present with unexplained alteration in the level of consciousness, especially if there is a prior history of epilepsy. The electroencephalogram plays a key role in the diagnosis and intravenous administration of diazepam is a useful diagnostic test, especially in conjunction with EEG. We present three patients recently diagnosed in Iceland.
Legriel, Stephane; Bruneel, Fabrice; Spreux-Varoquaux, Odile; Birenbaum, Aurelie; Chadenat, Marie Laure; Mignon, François; Abbosh, Nathalie; Henry-Lagarrigue, Matthieu; Revault D'Allonnes, Laure; Guezennec, Pierre; Troche, Gilles; Bedos, Jean Pierre
Posterior reversible encephalopathy syndrome (PRES) is known to occur in association with several substances. However, lysergic acid amide (LSA) is not among the previously reported causes of PRES. We report on a patient with PRES presenting as convulsive status epilepticus associated with hypertensive encephalopathy after LSA ingestion. Magnetic resonance imaging was performed and catecholamine metabolites assayed. The patient achieved a full recovery after aggressive antihypertensive therapy and intravenous anticonvulsivant therapy. The clinical history, blood and urinary catecholamine levels, and response to treatment strongly suggest that PRES was induced by LSA. LSA, a hallucinogenic agent chiefly used for recreational purposes, should be added to the list of causes of PRES.
Kenney-Jung, Daniel L.; Kahoud, Robert J.; Vezzani, Annamaria; LaFrance-Corey, Reghann G.; Ho, Mai-Lan; Muskardin, Theresa Wampler; Gleich, Stephen J.; Wirrell, Elaine C.; Howe, Charles L.; Payne, Eric T.
Febrile infection-related epilepsy syndrome (FIRES) is a devastating epileptic encephalopathy with limited treatment options and an unclear etiology. Anakinra is a recombinant version of the human interleukin-1 receptor antagonist used to treat autoinflammatory disorders. This is the first report of anakinra for treatment of a child with super-refractory status epilepticus secondary to FIRES. Anakinra was well-tolerated and effective. Cerebral spinal fluid analysis revealed elevated levels of proinflammatory cytokines before treatment that normalized on anakinra, suggesting a potential pathogenic role for neuroinflammation in FIRES. Further studies are required to assess anakinra efficacy and dosing, and to further delineate disease etiology. PMID:27770579
Greco, Filippo; Cocuzza, Maria Donatella; Smilari, Pierluigi; Sorge, Giovanni; Pavone, Lorenzo
Children with acute encephalopathy show prolonged electrographic seizure activity consistent with nonconvulsive status epilepticus (NCSE). Pediatric NCSE is a heterogeneous clinical entity with poor outcome and different etiologies, including central nervous system infection, stroke, toxic-metabolic syndrome, and epileptic syndrome. We report a 4-year-old girl with seizure and behavioral changes in whom the analysis of cerebrospinal fluid by polymerase chain reaction was positive for Epstein-Barr virus. We emphasize the importance of electroencephalography (EEG), and particularly, of continuous EEG monitoring for early recognition and appropriate treatment of this condition. PMID:24744940
Charalambous, M; Bhatti, S F M; Van Ham, L; Platt, S; Jeffery, N D; Tipold, A; Siedenburg, J; Volk, H A; Hasegawa, D; Gallucci, A; Gandini, G; Musteata, M; Ives, E; Vanhaesebrouck, A E
Intranasal administration of benzodiazepines has shown superiority over rectal administration for terminating emergency epileptic seizures in human trials. No such clinical trials have been performed in dogs. To evaluate the clinical efficacy of intranasal midazolam (IN-MDZ), via a mucosal atomization device, as a first-line management option for canine status epilepticus and compare it to rectal administration of diazepam (R-DZP) for controlling status epilepticus before intravenous access is available. Client-owned dogs with idiopathic or structural epilepsy manifesting status epilepticus within a hospital environment were used. Dogs were randomly allocated to treatment with IN-MDZ (n = 20) or R-DZP (n = 15). Randomized parallel-group clinical trial. Seizure cessation time and adverse effects were recorded. For each dog, treatment was considered successful if the seizure ceased within 5 minutes and did not recur within 10 minutes after administration. The 95% confidence interval was used to detect the true population of dogs that were successfully treated. The Fisher's 2-tailed exact test was used to compare the 2 groups, and the results were considered statistically significant if P < .05. IN-MDZ and R-DZP terminated status epilepticus in 70% (14/20) and 20% (3/15) of cases, respectively (P = .0059). All dogs showed sedation and ataxia. IN-MDZ is a quick, safe and effective first-line medication for controlling status epilepticus in dogs and appears superior to R-DZP. IN-MDZ might be a valuable treatment option when intravenous access is not available and for treatment of status epilepticus in dogs at home. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Cross, J Helen
Status epilepticus is recognised as an acute emergency requiring urgent intervention. The optimal timing of such an intervention during a prolonged seizure, and the reasons for such, have provided much discussion. For operational purposes, a definition of a prolonged seizure of ≥5 minutes requiring intervention appears justified. However, a definition of status epilepticus of ≥30 minutes should stand, with the proportion of seizures proceeding to this clinical state remaining small. The reasons for this may be inherent to an individual, but an understanding of the mechanisms underlying the predisposition may lead to improved management pathways in the future.
Shelton, Chasity M; Alford, Elizabeth L; Storgion, Stephanie; Wheless, James; Phelps, Stephanie J
We describe the use of topiramate in a healthy 12-year-old (88-kg) male who developed refractory generalized convulsive status epilepticus. Seizures persisted despite aggressive use of benzodiazepines (intravenous lorazepam; oral clorazepate), barbiturates (i.e., phenobarbital, pentobarbital), and hydantoins. The child's seizures were controlled with nasogastrically administered topiramate in doses up to 500 mg twice daily (11.4 mg/kg/day). The patient did not display any clinical or laboratory signs of metabolic acidosis while receiving topiramate. Topiramate should be considered as a treatment option in refractory status epilepticus.
Shelton, Chasity M.; Alford, Elizabeth L.; Storgion, Stephanie; Wheless, James
We describe the use of topiramate in a healthy 12-year-old (88-kg) male who developed refractory generalized convulsive status epilepticus. Seizures persisted despite aggressive use of benzodiazepines (intravenous lorazepam; oral clorazepate), barbiturates (i.e., phenobarbital, pentobarbital), and hydantoins. The child's seizures were controlled with nasogastrically administered topiramate in doses up to 500 mg twice daily (11.4 mg/kg/day). The patient did not display any clinical or laboratory signs of metabolic acidosis while receiving topiramate. Topiramate should be considered as a treatment option in refractory status epilepticus. PMID:25762878
Ibrahim, Tarik F; Sweis, Rochelle T; Nockels, Russ P
Postoperative vision loss (POVL) is a devastating complication and has been reported after complex spine procedures. Anterior ischemic optic neuropathy and posterior optic neuropathy are the 2 most common causes of POVL. Bilateral occipital lobe seizures causing complete blindness are rare and have not been reported as a cause of POVL after spine surgery with the patient prone. The authors report the case of a 67-year-old man without a history of seizures who underwent a staged thoracolumbar deformity correction and developed POVL 6 hours after surgery. Imaging, laboratory, and ophthalmological examination results were nonrevealing. Routine electroencephalography study results were negative, but continuous electroencephalography captured bilateral occipital lobe seizures. The patient developed nonconvulsive status epilepticus despite initial treatment with benzodiazepines and loading doses of levetiracetam and lacosamide. He was therefore intubated for status epilepticus amauroticus and received a midazolam infusion. After electrographic seizure cessation for 48 hours, the patient was weaned off midazolam. The patient was maintained on levetiracetam and lacosamide without seizure recurrence and returned to his preoperative visual baseline status.
Barzegar, Mohammad; Mahdavi, Mohammad; Galegolab Behbehani, Afshin; Tabrizi, Aidin
Refractory status epilepticus (RSE) is a life-threatening disease in children wherein the patient's convulsive seizures do not respond to adequate initial anticonvulsants. RSE is associated with high rate of mortality and morbidity. This study was aimed to survey the risk factors leading status epilepticus (SE) to RSE in children, and their early outcome. Patients with SE hospitalized in Tabriz Children's Hospital, Iran were studied during the years 2007 and 2008 with regard to their clinical profile, etiology, the treatment methods available to them and their outcome upon release from the hospital. Among 132 patients with SE, 53 patients (40.15%) suffered from RSE. Acute symptomatic etiology was a risk factor responsible for developing RSE in the patient (P=0.004). Encephalitis was the most common etiology of acute symptomatic SE. There was no significant relationship observed between RSE and the patients' age, gender, date of initial drug intake and type of seizure. The mortality rate was 8.3% and a new neurological deficit occurred in 25.7% of cases. None of RSE with encephalitis returned to the baseline status. Mortality and morbidity rates were significantly higher in children with RSE than in those with SE (P=0.006). Etiology of SE significantly influenced prognosis of it with significant incidence of RSE in acute symptomatic group. Because acute neurological insult such as encephalitis and meningitis are common causes of RSE in children, properly management of them is necessary to avoid permanent brain damage.
Eue, S; Grumbt, M; Müller, M; Schulze, A
Since its introduction in 2006, 43 patients with various forms of status epilepticus (SE) have been treated with the intravenous formulation of levetiracetam (LEV) in our clinic. After ineffective treatment with benzodiazepines, intravenous LEV was administered as a short infusion (nonconvulsive and subtle SE) at a dose of 1000 or 2000 mg. In cases of convulsive SE, a fractionated injection of 1000 or 2000 mg was used. When the results for both are combined, SE could be terminated in 19 of 43 patients. Intravenous LEV was more effective in simple focal SE (3/5), complex focal SE (11/18) and myoclonic status (2/2) than in nonconvulsive (2/8) and subtle (1/2) SE. In no case was (secondarily) generalized convulsive status epilepticus (0/8) terminated. Intravenous LEV was also well-tolerated when injected in fractionated form. No severe adverse reactions were observed. As a result of this investigation, intravenous LEV in moderate doses may represent an efficacious and well-tolerated alternative for the treatment of focal (simple and complex focal) and myoclonic SE. Further investigations are needed to confirm this assumption as the patient numbers are quite low.
Ozkaya, Gülşen; Kurne, Asli; Unal, Serhat; Oğuz, Kader Karli; Karabudak, Rana; Saygi, Serap
We describe an HIV-infected, bilingual patient presenting with Wernicke's aphasia due to partial status epilepticus with periodic lateralized epileptiform discharges, as the first sign of AIDS-toxoplasmosis complex. The localization of the native and secondary language centers in the brain and the possible role of recurrent seizures in the fluctuating course of Wernicke's aphasia in this patient are discussed. The clinical course of this patient supports the belief that a second language area for a second language learned in the later stages of life is located in an area different from that for the native language but still in close proximity to it.
Hassan, Haseeb; Rajiv, Keni Ravish; Menon, Ramshekhar; Menon, Deepak; Nair, Muralidharan; Radhakrishnan, Ashalatha
Status epilepticus is a neurological emergency with significant morbidity and mortality. This study describes the clinical profile, treatment, and predictors of outcome of status epilepticus in a tertiary referral centre in a developing country and aims to highlight the similarities and differences from data available from the western world. A retrospective analysis of data of patients treated for status epilepticus was conducted from prospectively maintained records, between January 2000 and September 2010. The demographic data, clinical profile and investigations (including neuroimaging and EEG), aetiology, treatment, and outcomes were studied and compared with data available from the western world. The analysis included 108 events in 84 patients. A single episode of status epilepticus was treated in 72 patients (86%) and multiple status epilepticus events, ranging from two to six per patient, were managed in 12 patients (14%). Mean age was 24.1±20.3 years and 63% were males. The types of status epilepticus included convulsive status in 98 (90.7%), non-convulsive status in seven (6.5%), and myoclonic status in three (2.8%). The majority of events (60%) were remote symptomatic, 16% were acute symptomatic, 16% were of unexplained aetiology, and 8% were progressive symptomatic. In 85 events (79%), status epilepticus could be aborted with first and second-line drugs. The remaining 23 events (21%) progressed to refractory status epilepticus, among which, 13 (56%) were controlled with continuous intravenous midazolam infusion. Case fatality rate was 11%, neurological sequelae were reported in 22%, and 67% returned to baseline. Acute symptomatic status, older age, altered sensorium at the time of admission, and delayed hospitalisation were predictors of poor outcome. Aetiology was the most important determinant of outcome of status epilepticus, as in reports from the western world, with remote symptomatic aetiology secondary to gliosis being the most common
Shah, Amish M; Vashi, Anita; Jagoda, Andy
Status epilepticus (SE) is divided into convulsive and non-convulsive types; both are associated with significant morbidity and mortality. Although convulsive SE is easily recognized, non-convulsive SE remains an elusive diagnosis as physical signs are varied and subtle. Successful management depends on a comprehensive approach that involves diagnostic testing and pharmacological interventions while ensuring cerebral oxygenation and perfusion at all times. There are a limited number of well-designed studies to support the development of evidence-based recommendations for the management of SE, especially for the management of non-convulsive status. Benzodiazepines, specifically lorazepam, continue to be the most commonly recommended first-line therapy; best treatment for refractory status cases depends on resources available and must be tailored to the individual institution. In order to facilitate care, it is recommended that each institution develop a management protocol for these patients.
Lucchi, Chiara; Vinet, Jonathan; Meletti, Stefano; Biagini, Giuseppe
Status epilepticus (SE) is one of the recognized primary precipitating events that can lead to temporal lobe epilepsy (TLE) associated with hippocampal sclerosis. This type of epilepsy is characterized by poor response to drug treatment, often requiring surgical intervention to remove the mesial temporal regions involved in the seizure onset. However, even neurosurgery may not be completely successful. Thus, the prevention of hippocampal damage and epileptogenesis is currently evaluated as a possible alternative therapeutic approach to prevent the development of pharmacoresistant TLE. Lines of evidence suggest that ischemic-hypoxic lesions might occur in different brain regions, including the hippocampus, during SE. Especially in the hippocampal CA3 region, an ischemic-like lesion develops in the stratum lacunosum-moleculare and is mainly characterized by a loss of astrocytes and neuronal processes and increased immunostaining of pimonidazole which probes areas exposed to hypoxia. Interestingly, these mechanisms can contribute to neuronal cell loss and may be counteracted by drugs that can afford vascular protection, as in the case of ligands of the ghrelin receptor. Notably, some of the ghrelin receptor ligands possess a double edge effect, since they are anticonvulsant and vascular-protective, thus, potentially representing new tools to counteract the consequences of SE. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.
Weiss, Erica F; Masur, David; Shinnar, Shlomo; Hesdorffer, Dale C; Hinton, Veronica J; Bonner, Melanie; Rinaldi, Julie; Van de Water, Virginia; Culbert, James; Shinnar, Ruth C; Seinfeld, Syndi; Gallentine, William; Nordli, Douglas R; Frank, L Mathew; Epstein, Leon; Moshé, Solomon L; Sun, Shumei
The objective of this study was to determine early developmental and cognitive outcomes of children with febrile status epilepticus (FSE) one month and one year after FSE. One hundred ninety four children with FSE were evaluated on measures of cognition, receptive language, and memory as part of the FEBSTAT study and compared with 100 controls with simple febrile seizures (FSs). Children with FSE did not differ dramatically on tasks compared with FS controls at one month after FSE but demonstrated slightly weaker motor development (p=0.035) and receptive language (p=0.034) at one year after FSE. Performances were generally within the low average to average range. Within the FSE cohort, non-White children performed weaker on many of the tasks compared with Caucasian children. At the one-year visit, acute hippocampal T2 findings on MRI were associated with weaker receptive language skills (p=0.0009), and human herpes virus 6 or 7 (HHV6/7) viremia was associated with better memory performances (p=0.047). Febrile status epilepticus does not appear to be associated with significant cognitive impairment on early developmental measures, although there is a trend for possible receptive language and motor delay one year after FSE. Further follow-up, which is in progress, is necessary to track long-term cognitive functioning. Copyright © 2016 Elsevier Inc. All rights reserved.
Gagnon, Maude-Marie; Savard, Martin; Mourabit Amari, Karim
Autoimmune encephalitis is an inflammatory disorder of the brain that may be associated with different neuronal antibodies. Recently, an increasing number of valuable autoantibodies have been identified, including GABAAR antibodies, which appear to be associated with a severe form of encephalitis with refractory status epilepticus. We report here on a patient with encephalitis associated with GAD65 and GABAAR antibodies, an entity that remains an understudied topic, with an unanticipated clinical presentation and we describe the longitudinal follow-up. We report a case of encephalitis associated with GAD65 and GABAAR antibodies; we describe clinical and paraclinical features and the longitudinal follow-up. Our case presented with dysgueusia, dysosmia and episodes of hyperventilation that evolved into a refractory status epilepticus. Multiple anticonvulsant drugs were required. An aggressive immunotherapy was associated with a relative favorable outcome, in regard of epilepsy and cognitive functions. However, a relapse occurred and a full recovery was not observed at the last follow-up visit. There was no correlation between GAD65 antibodies titers and disease activity. Autoimmune encephalitis associated with GABAAR and GAD65 antibodies might be a severe and refractory disease. The appropriate treatment is currently unknown for those patients. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Rossetti, Andrea O; Lowenstein, Daniel H
Refractory status epilepticus (RSE) is defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. RSE should be treated promptly to prevent morbidity and mortality; however, scarce evidence is available to support the choice of specific treatments. Major independent outcome predictors are age (not modifiable) and cause (which should be actively targeted). Recent recommendations for adults suggest that the aggressiveness of treatment for RSE should be tailored to the clinical situation. To minimise intensive care unit-related complications, focal RSE without impairment of consciousness might initially be approached conservatively; conversely, early induction of pharmacological coma is advisable in generalised convulsive forms of the disorder. At this stage, midazolam, propofol, or barbiturates are the most commonly used drugs. Several other treatments, such as additional anaesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (eg, electroconvulsive treatment or hypothermia), have been used in protracted RSE. Treatment lasting weeks or months can sometimes result in a good outcome, as in selected patients after encephalitis or autoimmune disorders. Well designed prospective studies of RSE are urgently needed. Copyright © 2011 Elsevier Ltd. All rights reserved.
Sivakumar, Sanjeev; Ibrahim, Mohammad; Parker, Dennis; Norris, Gregory; Shah, Aashit; Mohamed, Wazim
Refractory status epilepticus (RSE) is a medical emergency, with significant morbidity and mortality. The use and effectiveness of clobazam, a unique 1,5-benzodiazepine, in the management of RSE has not been reported before. Over the last 24 months, we identified 17 patients with RSE who were treated with clobazam in our hospital. Eleven of the 17 patients had prior epilepsy. Fifteen patients had focal status epilepticus. Use of clobazam was prompted by a favorable pharmacokinetic profile devoid of drug interactions. Clobazam was introduced after a median duration of 4 days and after a median of three failed antiepileptic drugs. A successful response, defined as termination of RSE within 24 h of administration, without addition or modification of concurrent AED and with successful wean of anesthetic infusions, was seen in 13 patients. Indeterminate response was seen in three patients, whereas clobazam was unsuccessful in one patient. Clobazam averted the need for anesthetic infusions in five patients. Clobazam was well tolerated, and appears to be an effective and promising option as add-on therapy in RSE. Its efficacy, particularly early in the course of SE, should be further investigated in prospective, randomized trials. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
Nam, Sook Hyun; Lee, Bo Lyun; Lee, Cha Gon; Yu, Hee Joon; Joo, Eun Yeon; Lee, Jeehun; Lee, Munhyang
Ketogenic diet (KD) is known to be effective in intractable epilepsy. However, the role of KD in refractory status epilepticus (RSE) has not been well described. The aim of this study is to explore the role of KD in patients with RSE. We retrospectively reviewed the medical records of four children and one adult with RSE between October 2006 and August 2010. All presented with status epilepticus (SE) that was presumed to be associated with viral encephalitis. After we failed to control the seizures with standard measures for SE, we tried KD. The overall seizure frequency decreased to <50% of baseline in median eight (1-19) days. At one month of KD, two patients were seizure-free, one patient showed >90% seizure reduction, and the others had >75% decrease without generalized seizures. With improvement in the RSE, we were able to taper the antiepileptic drugs (AEDs) and wean patients from prolonged mechanical ventilation. The adverse events of KD in RSE included aspiration pneumonia, gastroesophageal reflux, constipation, and hypertriglyceridemia. Those results demonstrate that KD can be a valuable therapeutic option for patients with RSE. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.
Jayalakshmi, Sita; Vooturi, Sudhindra; Sahu, Sambit; Yada, Praveen Kumar; Mohandas, Surath
We aimed to evaluate the determinants of outcome in new onset refractory status epilepticus (SE). A retrospective analysis of patients with new onset SE admitted between May 2005 and October 2013 was performed. Regression analysis was used to determine factors that affect progression of new onset SE to refractory status epilepticus (RSE) and mortality. Among 114 patients with new onset SE, 52 patients progressed to RSE. Sixty seven (58.7%) were men. New onset RSE patients were younger than new onset SE patients (mean 35.9 ± standard deviation18.2 versus 28.7 ± 20.2 years; p=0.050). Cryptogenic aetiology was the most significant determinant of progression of new onset SE to RSE (Exp [β]=5.68; p=0.001). The overall mortality in the entire group was 23.7%, significantly higher in new onset RSE group (40.4% versus 9.7%; p<0.0001). New onset RSE patients with symptomatic and cryptogenic etiology did not differ for clinical characteristics and outcome. Acidosis was the strongest predictor of mortality in the entire cohort (Exp [β]=8.72; p=0.005). Nearly half of the patients with new onset SE progressed to RSE. While cryptogenic aetiology determined progression of new onset SE to RSE, acidosis was associated with mortality. The outcome was similar between symptomatic and cryptogenic new onset RSE. Copyright © 2015 Elsevier Ltd. All rights reserved.
Ebrahem, Rawaa; Cooper, Scott; Manlove, Emily; Lee, Ricky
Posterior reversible encephalopathy syndrome (PRES) is a neurological condition characterized by headaches, visual disturbances, and seizures. A magnetic resonance imaging (MRI) scan of an affected brain typically shows symmetrical white matter edema in the posterior cerebral hemispheres. The onset of PRES can constitute a medical emergency, especially when accompanied by status epilepticus. If promptly recognized and treated, the clinical syndrome and associated radiological findings are usually resolved in a matter of weeks or months. Carfilzomib is a proteasome inhibitor that is newly approved for relapsing myeloma in a patient who has received one or more lines of therapy. In this paper, we report on a 52-year-old female on carfilzomib for multiple myeloma who developed PRES following her second dose of treatment. She was admitted for chronic obstructive pulmonary disease (COPD) exacerbation, and while she was in the hospital, she developed a severe headache, blindness, and status epilepticus. A brain MRI showed signs consistent with PRES. After carfilzomib was discontinued, her symptoms resolved within three days. Unfortunately, the patient passed away shortly after being discharged, so there was no opportunity to perform a repeat MRI. PMID:28357173
Husain, A; Horn, G; Jacobson, M
Background: Non-convulsive status epilepticus (NCSE) is status epilepticus without obvious tonic–clonic activity. Patients with NCSE have altered mental state. An EEG is needed to confirm the diagnosis, but obtaining an EEG on every patient with altered mental state is not practical. Objective: To determine whether clinical features could be used to predict which patients were more likely to be in NCSE and thus in need of an urgent EEG. Methods: Over a six month period, all patients for whom an urgent EEG was ordered to identify NCSE were enrolled. Neurology residents examined the patients and filled out a questionnaire without knowledge of the EEG results. The patients were divided into two groups, NCSE and non-NCSE, depending on the EEG result. The clinical features were compared between the two groups. The sensitivity and specificity of the features were calculated. Results: 48 patients were enrolled, 12 in NCSE and 36 not in NCSE. Remote risk factors for seizures, severely impaired mental state, and ocular movement abnormalities were seen significantly more often in the NCSE group. The combined sensitivity of remote risk factors for seizures and ocular movement abnormalities was 100%. Conclusions: There are certain clinical features that are more likely to be present in patients in NCSE compared with other types of encephalopathy. Either remote risk factors for seizures or ocular movement abnormalities were seen in all patients in NCSE. These features may be used to select which patients should have an urgent EEG. PMID:12531946
Sechi, GianPietro; De Riu, Pierluigi; Mameli, Ombretta; Deiana, Giovanni A; Cocco, Giovanni A; Rosati, Giulio
The objective of this study was to document the convulsant properties of thiocolchicoside in rats, and to characterise the electroclinical pattern of epileptic seizures. Experiments were carried out in three groups of male Wistar rats: in group A, thiocolchicoside was applied topically to the pia, or given by microinjection to the cerebral cortex (2 microg/microl); in group B, the drug was administered parenterally (6 mg/kg) to rats with minimal lesions of the dura and arachnoid membranes; in group C, thiocolchicoside was administered parenterally (up to 12 mg/kg) to intact rats. In all animals, electroclinical activity was continuously monitored for at least 3 hours after thiocolchicoside injection or application. In group A, electrographic and behavioural activity of focal motor seizures occurred in 100% of animals, developing into a focal status epilepticus; in group B, a multifocal epileptic pattern with secondary generalisation, clinically characterised by clonic or tonic-clonic seizures occurred in 100% of animals, until a secondarily generalised convulsive status epilepticus; in group C, none of animals showed either electrographic or behavioural seizure activity. Our study documents that thiocolchicoside has a powerful convulsant activity in the rat, perhaps due to an antagonistic interaction of the compound with a cortical subtype of the GABA(A) receptor.
Shao, Yi-ye; Li, Bing; Huang, Yong-mei; Luo, Qiong; Xie, Yang-mei; Chen, Ying-hui
Abstract Aim Status epilepticus (SE) results in the generation of reactive oxygen species (ROS), which contribute to seizure-induced brain injury. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Thymoquinone (TQ) is a bioactive monomer extracted from black cumin (Nigella sativa) seed oil that has anti-inflammatory, anti-cancer, and antioxidant activity in various diseases. This study evaluated the protective effects of TQ on brain injury in a lithium-pilocarpine rat model of SE and investigated the underlying mechanism related to antioxidative pathway. Methods Electroencephalogram and Racine scale were used to value seizure severity. Passive-avoidance test was used to determine learning and memory function. Moreover, anti-oxidative activity of TQ was observed using Western blot and super oxide dismutase (SOD) activity assay. Results Latency to SE increased in the TQ-pretreated group compared with rats in the model group, while the total power was significantly lower. Seizure severity measured on the Racine scale was significantly lower in the TQ group compared with the model group. Results of behavioral experiments suggest that TQ may also have a protective effect on learning and memory function. Investigation of the protective mechanism of TQ showed that TQ-pretreatment significantly increased the expression of Nrf2, HO-1 proteins and SOD in the hippocampus. Conclusion These findings showed that TQ attenuated brain injury induced by SE via an anti-oxidative pathway. PMID:28400978
Wiss, Adam L; Samarin, Michael; Marler, Jacob; Jones, G Morgan
Status epilepticus requires treatment with emergent initial therapy with a benzodiazepine and urgent control therapy with an additional antiepileptic drug (AED) to terminate clinical and/or electrographic seizure activity. However, nearly one-third of patients will prove refractory to the aforementioned therapies and are prone to a higher degree of neuronal injury, resistance to pharmacotherapy, and death. Current guidelines for refractory status epilepticus (RSE) recommend initiating a continuous intravenous (CIV) anesthetic over bolus dosing with a different AED. Continuous intravenous agents most commonly used for this indication include midazolam, propofol, and pentobarbital, but ketamine is an alternative option. Comparative studies illustrating the optimal agent are lacking, and selection is often based on adverse effect profiles and patient-specific factors. In addition, dosing and titration are largely based on small studies and expert opinion with continuous electroencephalogram monitoring used to guide intensity and duration of treatment. Nonetheless, the doses required to halt seizure activity are likely to produce profound adverse effects that clinicians should anticipate and combat. The purpose of this review was to summarize the available RSE literature focusing on CIV midazolam, pentobarbital, propofol, and ketamine, and to serve as a primer for nurses providing care to these patients.
Loddenkemper, Tobias; Fernández, Iván Sánchez; Peters, Jurriaan M
Continuous spike and waves during sleep is an age-related epileptic encephalopathy that presents with neurocognitive regression, seizures, and an EEG pattern of electrical status epilepticus during sleep. Patients usually present around 5 years of age with infrequent nocturnal unilateral motor seizures that progress within 1 to 2 years to a severe epileptic encephalopathy with frequent seizures of different types, marked neurocognitive regression, and an almost continuous spike-wave EEG pattern during slow-wave sleep. The pathophysiology of continuous spike and waves during sleep is not completely understood, but the corticothalamic neuronal network involved in physiologic oscillating patterns of sleep is thought to be switched into a pathologic discharging mode. Early developmental injury and/or genetic predisposition may play a role in the potentiation of age-related hyperexcitability in the immature brain. A better understanding of the mechanisms leading to electrical status epilepticus during sleep may provide additional therapeutic targets that can improve the outcome of seizures, EEG pattern, and cognitive development in patients with continuous spike and waves during sleep.
Pinchefsky, Elana F; Hahn, Cecil D
Increasing recognition of electrographic seizures and electrographic status epilepticus in critically ill neonates and children has highlighted the importance of identifying their potential contributions to neurological outcomes to guide optimal management. Recent studies in children and neonates have found an independent association between increasing seizure burden and worse short-term and long-term outcomes, even after adjusting for other important contributors to outcome such as seizure cause and illness severity. The risk of worse neurological outcome has been shown to increase above a seizure burden threshold of 12-13 min/h, which is considerably lower than the conventional definition of status epilepticus of 30 min/h. Randomized controlled trials in neonates have demonstrated that electroencephalography-targeted therapy can successfully reduce seizure burden, but due to their small size these trials have not been able to demonstrate that more aggressive electroencephalography-targeted treatment of both subclinical and clinical seizures results in improved outcome. Despite mounting evidence for an independent association between increasing seizure burden and worse outcome, further study is needed to determine whether early seizure identification and aggressive antiseizure treatment can improve neurodevelopmental outcomes.
Johnson, Kara B; Michelson, Kenneth A; Lyons, Todd W; Nigrovic, Lise E; Landschaft, Assaf; Loddenkemper, Tobias; Kimia, Amir A
To determine the rate of cerebrospinal fluid (CSF) pleocytosis among children presenting with status epilepticus (SE) without proven central nervous system infection. We performed a retrospective cross-sectional study of all patients aged one month to 21 years of age who were evaluated in a single pediatric emergency department (ED) for SE between 1995 and 2012. We limited our study to those children who had a CSF culture obtained and excluded those children with proven viral or bacterial infection. We defined SE in a patient who had a single seizure or a cluster of seizures without regaining consciousness which lasted 30 min or longer. We defined CSF pleocytosis as a CSF white blood cells (WBC)>10 cells/mm(3) and a peripheral leukocytosis as WBC ≥ 15,000 cells/mm(3). We compared the rate of CSF pleocytosis between children with and without peripheral leukocytosis using the Fisher's exact test. We identified 289 ED visits for SE, of which 178 (62%) met study inclusion criteria. Seven children (4%, 95% confidence interval 1.7-8.2%) had CSF pleocytosis. More children with peripheral leukocytosis had CSF pleocytosis: (8.6% with peripheral leukocytosis vs. 0.9% without leukocytosis, p=0.01). CSF pleocytosis is relatively uncommon among children with prolonged seizures, even in the presence of peripheral leukocytosis. Therefore, all children with CSF pleocytosis after status epilepticus need comprehensive evaluation for central nervous system infection. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Kravljanac, Ruzica; Djuric, Milena; Jankovic, Borisav; Pekmezovic, Tatjana
evaluation of etiology, clinical course and response to the treatment of status epilepticus (SE) in children, with particular investigation of superrefractory SE. The retrospective study included children with convulsive SE aged 0.2-18 years, treated from 1995 to 2011. Status epilepticus is defined as a continuous seizure or intermittent seizures without full recovery of consciousness between seizures for at least 30 min. Refractory SE is diagnosed if SE lasts for more than 60 min, while superrefractory SE if SE continues or recurs 24 h or more after the onset of an anesthesia therapy, including those cases that recur after reduction or withdrawal of an anesthesia. The etiology was summarized in five categories: idiopathic/cryptogenic, remote symptomatic, febrile SE, acute symptomatic and progressive encephalopathy. The patients were treated according to the same hospital protocol. Midazolam iv and diazepam rectally were given as the first line drugs, phenobarbital/phenytoin iv as the second line drugs. If they failed, third line drugs, midazolam and thiopental were given in continuous intravenous infusion. The medication was defined as effective if seizure clinically stopped within 20 min, without recurrence within the next 6 h. Midazolam was assessed as effective even if it failed as the first line, but was effective in intravenous infusion as the third line drug. The study consisted of 602 SE in 395 children. There were 305 (50.7%) refractory SE episodes, and 43 (7.1%) of superrefractory SE. Idiopathic/cryptogenic and febrile SE was the most common etiology in the first SE, while progressive encephalopathy and remote symptomatic was in recurrent and superrefractory SE. The most effective drugs were: midazolam (306/339) given in mean dose of 0.4 mg/kg (range 0.1-1.2 mg/kg), thiopental (47/57) in mean dose of 4 mg/kg (range 3-5 mg/kg), phenobarbital (91/135) in dose of 20 mg/kg. Midazolam successfully stopped 306/339 SE episodes (90.3%), 67 SE (21.9%) by
de la Morena Vicente, M A; Granizo Martínez, J J; Ojeda Ruiz de Luna, J; Peláez Hidalgo, A; Luque Alarcón, M; Navacerrada Barrero, F J; Al Hussayni Husseini, S; García Cobos, E; Ballesteros Plaza, L; de Las Casas Cámara, G; Viudez Jiménez, I
Status epilepticus (SE) is a neurological emergency associated with significant mortality and morbidity. We analyse characteristics of this entity in our population. Data from electronic medical records of adults diagnosed with SE were collected retrospectively from 5 hospitals over 4 years. Data reflected 84 episodes of SE in 77 patients with a mean age of 60.3 years. Of this sample, 52.4% had a previous history of epilepsy. Status classification: 47.6% tonic-clonic, 21.4% complex partial, 17.9% partial motor, 6% partial simple, 3.6% myoclonic, and 3.6% subtle SE. Based on the duration of the episode, SE was defined in this study as early stage (up to 30min) in 13.1%, established (30-120min) in 20.2%, refractory (more than 120min) in 41.7%, and super-refractory (episodes continuing or recurring after more than 24h of anaesthesia) in 13.1%. Ten patients (11.9%) died when treatment failed to control SE. The cumulative percentage of success achieved was 8.3% with the first treatment, 27.3% for the second, 48.7% for the third, 58.2% for the fourth, 70.1% for the fifth, 80.8% for the sixth, 83.2% for the seventh, and 84.4% for the eighth. In our study, we found that SE did not respond to treatment within 2h in approximately half the cases and 11.9% of the patients died without achieving seizure control, regardless of the type of status. Half the patients responded by the third treatment but some patients needed as many as 8 treatments to resolve seizures. Using large registers permitting analysis of the different types and stages of SE is warranted. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.
Lucchi, Chiara; Curia, Giulia; Vinet, Jonathan; Gualtieri, Fabio; Bresciani, Elena; Locatelli, Vittorio; Torsello, Antonio; Biagini, Giuseppe
In models of status epilepticus ghrelin displays neuroprotective effects mediated by the growth hormone secretagogue-receptor 1a (GHS-R1a). This activity may be explained by anticonvulsant properties that, however, are controversial. We further investigated neuroprotection and the effects on seizures by comparing ghrelin with a more effective GHS-R1a agonist, JMV-1843. Rats were treated either with ghrelin, JMV-1843 or saline 10 min before pilocarpine, which was used to induce status epilepticus. Status epilepticus, developed in all rats, was attenuated by diazepam. No differences were observed among the various groups in the characteristics of pilocarpine-induced seizures. In saline group the area of lesion, characterized by lack of glial fibrillary acidic protein immunoreactivity, was of 0.45±0.07 mm2 in the hippocampal stratum lacunosum-moleculare, and was accompanied by upregulation of laminin immunostaining, and by increased endothelin-1 expression. Both ghrelin (P<0.05) and JMV-1843 (P<0.01) were able to reduce the area of loss in glial fibrillary acidic protein immunostaining. In addition, JMV-1843 counteracted (P<0.05) the changes in laminin and endothelin-1 expression, both increased in ghrelin-treated rats. JMV-1843 was able to ameliorate neuronal survival in the hilus of dentate gyrus and medial entorhinal cortex layer III (P<0.05 vs saline and ghrelin groups). These results demonstrate diverse protective effects of growth hormone secretagogues in rats exposed to status epilepticus. PMID:24015271
Shorvon, Simon; Ferlisi, Monica
Super-refractory status epilepticus is defined as status epilepticus that continues or recurs 24 h or more after the onset of anaesthetic therapy, including those cases where status epilepticus recurs on the reduction or withdrawal of anaesthesia. It is an uncommon but important clinical problem with high mortality and morbidity rates. This article reviews the treatment approaches. There are no controlled or randomized studies, and so therapy has to be based on clinical reports and opinion. The published world literature on the following treatments was critically evaluated: anaesthetic agents, anti-epileptic drugs, magnesium infusion, pyridoxine, steroids and immunotherapy, ketogenic diet, hypothermia, emergency resective neurosurgery and multiple subpial transection, transcranial magnetic stimulation, vagal nerve stimulation, deep brain stimulation, electroconvulsive therapy, drainage of the cerebrospinal fluid and other older drug therapies. The importance of treating the identifying cause is stressed. A protocol and flowchart for managing super-refractory status epilepticus is suggested. In view of the small number of published reports, there is an urgent need for the establishment of a database of outcomes of individual therapies.
Ferlisi, Monica; Shorvon, Simon
In a previous paper, we reviewed the range of therapies available for the treatment of super-refractory status epilepticus. Here we report a review of the outcome of therapies in refractory and super-refractory status epilepticus. Patients (n = 1168) are reported who had therapy with: thiopental, pentobarbital, midazolam, propofol, ketamine, inhalational anaesthetics (isoflurane, desflurane), antiepileptic drugs (topiramate, lacosamide, pregabalin, levetiracetam), hypothermia, magnesium, pyridoxine, immunotherapy, ketogenic diet, emergency neurosurgery, electroconvulsive therapy, cerebrospinal fluid drainage, vagal nerve stimulation and deep brain stimulation. The outcome parameters reported include control of status epilepticus, relapse on withdrawal, breakthrough seizures and mortality. Where reported (596 cases), the long-term outcome was found to be death (35%), severe neurological deficit (13%), mild neurological deficit (13%), undefined deficit (4%) and recovery to baseline (35%). The quality of reported outcome data is generally poor and the number of cases reported for all non-anaesthetic therapies is low. Outcome assessment is complicated by changes in co-medication, delay in response and publication bias. Given these deficits, only broad recommendations can be made regarding optimal therapy. An approach to therapy, divided into first-line, second-line and third-line therapy, is suggested on the basis of this outcome evaluation. The importance of treatments directed at the cause of the status epilepticus, and of supportive ITU care is also emphasized.
Zhao, Zi-Yu; Wang, Hong-Ying; Wen, Bin; Yang, Zhi-Bo; Feng, Kang; Fan, Jing-Chun
Midazolam, lorazepam, and diazepam were recommended as emergent initial therapy for status epilepticus. However, there are no current studies to confirm the best agent for pediatric status epilepticus. We compared the efficacy of midazolam, lorazepam, and diazepam in treating pediatric status epilepticus using a network meta-analysis method. In total, 16 randomized controlled trials containing 1821 patients were included. Nonintravenous midazolam, intravenous lorazepam, and intravenous diazepam were more successful in achieving seizure cessation when compared with nonintravenous diazepam (odds ratio = 2.23, 95% credibility interval: 1.62, 3.10; odds ratio = 2.71, 95% credibility interval: 1.25, 5.89; odds ratio = 2.65, 95% credibility interval: 1.12, 6.29; respectively). Among lorazepam, midazolam, and diazepam, midazolam had the highest probability (surface under the cumulative ranking area [SUCRA] = 0.792) of achieving seizure cessation, and lorazepam had the largest probability (surface under the cumulative ranking area = 0.4346) of being the best treatment in reduction of respiratory depression. In conclusion, nonintravenous midazolam and intravenous lorazepam were superior to intravenous or nonintravenous diazepam, and intravenous lorazepam was at least as effective as nonintravenous midazolam in treating pediatric status epilepticus. © The Author(s) 2016.
Taupin, Daniel; Racela, Rikki; Friedman, Daniel
We present a patient with peritoneal carcinosarcoma who was treated with the alkylating agent ifosfamide and experienced a rapid decline in mental status. Electroencephalogram (EEG) displayed generalized periodic epileptiform discharges, which raised suspicion for nonconvulsive status epilepticus (NCSE). Following administration of midazolam, the patient's clinical condition and EEG improved. We review the 8 documented cases of ifosfamide-induced NCSE, and demonstrate the similarity in clinical features when compared with ifosfamide neurotoxicity that is not classified as NCSE. EEG findings suggesting an ictal pattern are subtle and heterogeneous, but they are essential for a diagnosis. Since it is unlikely that EEGs are uniformly obtained in instances of ifosfamide neurotoxicity, many cases of NCSE may go unrecognized.
Postnikova, T Y; Zubareva, O E; Kovalenko, A A; Kim, K K; Magazanik, L G; Zaitsev, A V
Cognitive deficits and memory loss are frequent in patients with temporal lobe epilepsy. Persistent changes in synaptic efficacy are considered as a cellular substrate underlying memory processes. Electrophysiological studies have shown that the properties of short-term and long-term synaptic plasticity in the cortex and hippocampus may undergo substantial changes after seizures. However, the neural mechanisms responsible for these changes are not clear. In this study, we investigated the properties of short-term and long-term synaptic plasticity in rat hippocampal slices 24 h after pentylenetetrazole (PTZ)-induced status epilepticus. We found that the induction of long-term potentiation (LTP) in CA1 pyramidal cells is reduced compared to the control, while short-term facilitation is increased. The experimental results do not support the hypothesis that status epilepticus leads to background potentiation of hippocampal synapses and further LTP induction becomes weaker due to occlusion, as the dependence of synaptic responses on the strength of input stimulation was not different in the control and experimental animals. The decrease in LTP can be caused by impairment of molecular mechanisms of neuronal plasticity, including those associated with NMDA receptors and/or changes in their subunit composition. Real-time PCR demonstrated significant increases in the expression of GluN1 and GluN2A subunits 3 h after PTZ-induced status epilepticus. The overexpression of obligate GluN1 subunit suggests an increase in the total number of NMDA receptors in the hippocampus. A 3-fold increase in the expression of the GluN2B subunit observed 24 h after PTZ-induced status epilepticus might be indicative of an increase in the proportion of GluN2B-containing NMDA receptors. Increased expression of the GluN2B subunit may be a cause for reducing the magnitude of LTP at hippocampal synapses after status epilepticus.
Pessoa, Daniella Tavares; da Silva, Eva Luana Almeida; Costa, Edbhergue Ventura Lola; Nogueira, Romildo Albuquerque
Western diets are high in saturated fat and low in omega-3. Certain animals cannot produce omega-3 from their own lipids, making it necessary for it to be acquired from the diet. However, omega-3s are important components of the plasma membrane, and altering their proportions can promote physical and chemical alterations in the membranes, which may modify neuronal excitability. These alterations occur in healthy individuals, as well as in patients with epilepsy who are more sensitive to changes in brain electrical activity. This study evaluated the effect of a diet supplemented with omega-3 on the basal brain electrical activity both before and during status epilepticus in rats. To evaluate the brain electrical activity, we recorded electrocorticograms (ECoG) of animals both with and without omega-3 supplementation before and during status epilepticus induced by pilocarpine. Calculation of the average brain wave power by a power spectrum revealed that omega-3 supplementation reduced the average power of the delta wave by 20% and increased the average power of the beta wave by 45%. These effects were exacerbated when status epilepticus was induced in the animals supplemented with omega-3. The animals with and without omega-3 supplementation exhibited increases in basal brain electrical activities during status epilepticus. The two groups showed hyperactivity, but no significant difference between them was noted. Even though the brain activity levels observed during status epilepticus were similar between the two groups, neuron damage to the animals supplemented with omega-3 was more slight, revealing the neuroprotective effect of the omega-3. Copyright © 2017. Published by Elsevier B.V.
Fernández-Torre, José L; Burgueño, Paula; Ballesteros, María A; Hernández-Hernández, Miguel A; Villagrá-Terán, Nuria; de Lucas, Enrique Marco
Fat embolism syndrome (FES) is a rare complication of long-bone fractures and joint reconstruction surgery. To the best of our knowledge, we describe the clinical, electrophysiological, neuroimaging, and neuropathological features of the first case of super-refractory nonconvulsive status epilepticus (sr-NCSE) secondary to fat embolism. An 82-year-old woman was transferred to our intensive care unit because of a sudden decrease of consciousness level, right hemiparesis, and acute respiratory failure in the early postoperative period of knee prosthesis surgery. Brain computed tomography (TC) including angio-CT and CT perfusion was normal. An urgent video-electroencephalography (v-EEG) evaluation showed continuous sharp-and slow-wave at 2.0-2.5 Hz in keeping with the diagnosis of generalized NCSE. Epileptiform discharges ceased after the administration of 5mg of intravenous diazepam, and background activity constituted by diffuse theta waves was observed without clinical improvement. Treatment with levetiracetam (1000 mg/day) and sedation with propofol and midazolam were initiated. Moreover, continuous v-EEG monitoring was also started. Despite antiepileptic therapy, epileptiform activity recurred after the interruption of profound sedation, and valproate and lacosamide were added during the ensuing days. Magnetic resonance imaging (MRI) disclosed small scattered foci of acute ischemic infarcts and diffuse petechiae involving the basal ganglia and pons and centrum semiovale in keeping with fat embolism. Super-refractory nonconvulsive status epilepticus remained without control for 2 weeks. Finally, the patient died. The clinical autopsy revealed a bilateral lung fat embolism associated with a hemorrhagic infarction in the left lower lobe. Fatty lesions were also seen in the intestine and pancreas. Scattered microscopic cerebral infarcts associated with fat emboli in the capillaries were noticed, affecting both supra- and infratentorial structures. In addition
Dragancea, Irina; Backman, Sofia; Westhall, Erik; Rundgren, Malin; Friberg, Hans; Cronberg, Tobias
Postanoxic electrographic status epilepticus (ESE) is considered a predictor of poor outcome in resuscitated patients after cardiac arrest (CA). Observational data suggest that a subgroup of patients may have a good outcome. This study aimed to describe the prevalence of ESE and potential clinical and electrographic prognostic markers. In this retrospective single study, we analyzed consecutive patients who suffered from CA, and who received temperature management and were monitored with simplified continuous EEG (cEEG) during a five-year period. The patients' charts and cEEG data were initially screened to identify patients with clinical seizures or ESE. The cEEG diagnosis of ESE was retrospectively reanalyzed according to strict criteria by a neurophysiologist blinded to patient outcome. The EEG background patterns prior to the onset of ESE, duration of ESE, presence of clinical seizures, and use of antiepileptic drugs were analyzed. The results of somatosensory-evoked potentials (SSEPs) and neuron-specific enolase (NSE) at 48 h after CA were described in all patients with ESE. Antiepileptic treatment strategies were not protocolized. Outcome was evaluated using the Cerebral Performance Category (CPC) scale at 6 months, and good outcome was defined as CPC 1-2. Of 127 patients, 41 (32%) developed ESE. Twenty-five patients had a discontinuous EEG background prior to ESE, and all died without regaining consciousness. Sixteen patients developed a continuous EEG background prior to the start of ESE, four of whom survived, three with CPC 1-2 and one with CPC 3 at 6 months. Among survivors, ESE developed at a median of 46 h after CA. All had preserved N20 peaks on SSEP and NSE values of 18-37 μg/l. Electrographic status epilepticus is common among comatose patients after cardiac arrest, with few survivors. A combination of a continuous EEG background prior to ESE, preserved N20 peaks on SSEPs, and low or moderately elevated NSE levels may indicate a good outcome. This
Power, Kjersti Nesheim; Flaatten, Hans; Gilhus, Nils Erik; Engelsen, Bernt A
To retrospectively study effect and safety of propofol treatment in adult refractory generalised tonic clonic status epilepticus. Therapy refractory status epilepticus (RSE) is defined as a status that does not respond to 1st or 2nd line of treatment. Different anaesthetics are used to treat RSE, but no definite recommendations or priority has been scientifically established. Propofol has been the preferred agent for treating RSE at our intensive care unit since 2001. We present treatment mode, effect and outcome in 18 patients with 27 consecutive cases of RSE treated 2001-2010. Fifteen patients had 1 episode, and 3 patients had 2, 3 and 7 episodes, respectively. Mortality risk for each case of RSE was estimated using the Simplified Acute Physiology (SAPS) II score. Probable trigger factors were identified for 22 of the 27 RSE episodes. In 16/27 episodes seizures lasted more than 2h before anaesthesia was induced. A mean total dose of 7885.1mg was given for a mean duration of 34.4h. Break through seizures occurred in 8 of the patients and in 2 episodes of RSE in one patient, i.e. 9/27 episodes of RSE. Propofol was changed to another anaesthetic agent in 2 episodes. Complications occurred in 17 of the RSE episodes, the most frequent was pneumonia (9/27). One patient had complications that could be related to a propofol infusion syndrome (PRIS). In 8 of 18 patients and 14/27 RSE episodes no sequelae occurred. Seven episodes were associated with mild and 4 with severe sequelae and 2 of the patients died. We found a trend only for SAPS II score being higher in patients with more severe sequelae. Our data support propofol as an effective anaesthetic for treating RSE. Close clinical observation for possible PRIS is warranted if propofol is given for more than 48h. Copyright © 2011 Elsevier B.V. All rights reserved.
BARZEGAR, Mohammad; MAHDAVI, Mohammad; GALEGOLAB BEHBEHANI, Afshin; TABRIZI, Aidin
Objective Refractory status epilepticus (RSE) is a life-threatening disease in children wherein the patient’s convulsive seizures do not respond to adequate initial anticonvulsants. RSE is associated with high rate of mortality and morbidity. This study was aimed to survey the risk factors leading status epilepticus (SE) to RSE in children, and their early outcome. Materials & Methods Patients with SE hospitalized in Tabriz Children’s Hospital, Iran were studied during the years 2007 and 2008 with regard to their clinical profile, etiology, the treatment methods available to them and their outcome upon release from the hospital. Results Among 132 patients with SE, 53 patients (40.15%) suffered from RSE. Acute symptomatic etiology was a risk factor responsible for developing RSE in the patient (P=0.004). Encephalitis was the most common etiology of acute symptomatic SE. There was no significant relationship observed between RSE and the patients’ age, gender, date of initial drug intake and type of seizure. The mortality rate was 8.3% and a new neurological deficit occurred in 25.7% of cases. None of RSE with encephalitis returned to the baseline status. Mortality and morbidity rates were significantly higher in children with RSE than in those with SE (P=0.006). Conclusion Etiology of SE significantly influenced prognosis of it with significant incidence of RSE in acute symptomatic group. Because acute neurological insult such as encephalitis and meningitis are common causes of RSE in children, properly management of them is necessary to avoid permanent brain damage. PMID:26664438
Du, Yifeng; Kemper, Timothy; Qiu, Jiange; Jiang, Jianxiong
Neuroinflammation is a common feature in nearly all neurological and some psychiatric disorders. Resembling its extraneural counterpart, neuroinflammation can be both beneficial and detrimental depending on the responding molecules. The overall effect of inflammation on disease progression is highly dependent on the extent of inflammatory mediator production and the duration of inflammatory induction. The time-dependent aspect of inflammatory responses suggests that the therapeutic time window for quelling neuroinflammation might vary with molecular targets and injury types. Therefore, it is important to define the therapeutic time window for anti-inflammatory therapeutics, as contradicting or negative results might arise when different treatment regimens are utilized even in similar animal models. Herein, we discuss a few critical factors that can help define the therapeutic time window and optimize treatment paradigm for suppressing the cyclooxygenase-2/prostaglandin-mediated inflammation after status epilepticus. These determinants should also be relevant to other anti-inflammatory therapeutic strategies for the CNS diseases. PMID:26689339
Vezzani, Annamaria; Dingledine, Raymond; Rossetti, Andrea O
Status epilepticus (SE) is a life-threatening neurological emergency often refractory to available treatment options. It is a very heterogeneous condition in terms of clinical presentation and causes, which besides genetic, vascular and other structural causes also include CNS or severe systemic infections, sudden withdrawal from benzodiazepines or anticonvulsants and rare autoimmune etiologies. Treatment of SE is essentially based on expert opinions and antiepileptic drug treatment per se seems to have no major impact on prognosis. There is, therefore, urgent need of novel therapies that rely upon a better understanding of the basic mechanisms underlying this clinical condition. Accumulating evidence in animal models highlights that inflammation ensuing in the brain during SE may play a determinant role in ongoing seizures and their long-term detrimental consequences, independent of an infection or auto-immune cause; this evidence encourages reconsideration of the treatment flow in SE patients. PMID:26312647
Chepurnov, S A; Chepurnova, N E; Redkozubova, O M; Saakian, S A
This review focuses on the modeling of status epilepticus in animal brain and modern data on the mechanisms of epileptical seizures initiation using the pilocarpine binding with the muscarinic cholinoreceptors (litium pilocarpine model). The character of epileptics seizures in developing brain and adult brain of rats were investigated. The lines of modulation and inhibition epileptics statues by sacricine and intranasal application of neuropeptide thyroliberin in ultra-low doses are demonstrated. The role of the short-term changes (signal regulated kinase signaling cascade, Kv 4.2 potassium channels, hippocampal and cortical spike-wave discharges) and the long-term changes (loss of selective type of interneurons, excitatory circuits by mossy fiber sprouting) that promotion the epileptic state and recurrent seizures in limbic structure are discussed.
Guilbert, J; Flamant, C; Hallalel, F; Doummar, D; Frata, A; Renolleau, S
We describe a case of a young child who lived in Hong Kong who presented with a severe epilepticus status after a return flight to Paris. Routine laboratory tests failed to establish a cause. Upon further questioning, the parents reported that the nanny had given an abdominal massage to the child with an unlabelled solution reported to have anti‐flatulence effects. Toxicological analysis of this solution revealed the presence of camphor. Although the highly toxic effects of camphor have long been established, the present case illustrates that camphor continues to be a source of paediatric exposure. This case highlights the importance of systematic questioning and recalls the extreme danger associated with camphor even when administered transcutaneously. PMID:18029526
Balakrishnan, S; Nidhi, G; Pandhi, P
The aim of this study was to determine the effect of the duration of pilocarpine-induced status epilepticus (SE) on subsequent cognitive function in rats. SE was induced by pilocarpine (320 mg/kg i.p.) and was terminated by injection of 1 mg/kg diazepam at 30, 60 and 90 min in 3 groups of 10 rats each. Cognitive function was tested by a passive avoidance task and was assessed at the baseline and on days 1, 7, 14 and 21 (post SE). It was found that cognitive function was disrupted on days 7, 14 and 21 post SE in rats who had SE for 60 and 90 min, whereas it was not affected in rats that had 30 min of SE. Hence, the duration of SE may affect future cognitive performance and mandates emergency treatment.
Bragazzi, Nicola Luigi; Bacigaluppi, Susanna; Robba, Chiara; Nardone, Raffaele; Trinka, Eugen; Brigo, Francesco
People increasingly use Google looking for health-related information. We previously demonstrated that in English-speaking countries most people use this search engine to obtain information on status epilepticus (SE) definition, types/subtypes, and treatment. Now, we aimed at providing a quantitative analysis of SE-related web queries. This analysis represents an advancement, with respect to what was already previously discussed, in that the Google Trends (GT) algorithm has been further refined and correlational analyses have been carried out to validate the GT-based query volumes. Google Trends-based SE-related query volumes were well correlated with information concerning causes and pharmacological and nonpharmacological treatments. Google Trends can provide both researchers and clinicians with data on realities and contexts that are generally overlooked and underexplored by classic epidemiology. In this way, GT can foster new epidemiological studies in the field and can complement traditional epidemiological tools.
Griffith, Carrie A; Hoffmann, Daniel E
To describe a case of status epilepticus believed to be a consequence of inadvertent intrathecal administration of cefazolin in a dog undergoing a myelogram. A 4-year-old, 6.5 kg, male neutered Dachshund was referred for evaluation of an acute onset hind limb paraparesis. While performing a lumbar myelogram, cefazolin was inadvertently injected into the ventral subarachnoid space. Subsequent refractory seizure activity was attributed to the epileptogenic effects of intrathecally administered cefazolin. Supportive therapy led to eventual complete recovery. Although epileptogenic effects of intrathecally administered cefazolin are well documented in the human and experimental animal model literature, to the authors' knowledge this has not been characterized in the veterinary literature. This case highlights the need to be diligent and mindful when one administers medications, and describes the management of a dog adversely affected as a consequence of a medical error. © Veterinary Emergency and Critical Care Society 2013.
Sánchez-Carpintero, R; Camino, R; Smeyers, P; Raspall-Chaure, M; Martínez-Bermejo, A; Ruiz-Falcó, M L; Verdú, A; Sanmarti, F X; Blanco, O; Santos Borbujo, J; Picó, G; Cebollero, M A
Prolonged seizures and status epilepticus are common neurological medical emergencies. Early and appropriate treatment is essential to reduce morbidity and mortality. Most seizures occur in the community, so parents and caregivers must be prepared for their management. Benzodiazepines (BZD) are the first-line drugs used, with rectal diazepam (DZPr) being the most commonly used in pre-hospital treatment in Spain. In September 2011, the European Medicines Agency (EMA) authorized the use of oromucosal midazolam (MDZb) for the treatment of prolonged acute convulsive seizures in patients aged 3 months to <18 years. MDZb has a rapid onset, short duration of effect, and avoids first-pass hepatic metabolism. MDZb has shown to be at least as or more effective than DZPr to stop the seizures. Buccal administration is easier and more socially accepted, especially in adolescents and adults. It is a safe drug with similar effects to other BZD; MDZb improves the overall cost-effectiveness of seizures management.
Tyler, Anna L; Mahoney, J Matthew; Richard, Gregory R; Holmes, Gregory L; Lenck-Santini, Pierre-Pascal; Scott, Rod C
Status epilepticus (SE) is a common neurological emergency, which has been associated with subsequent cognitive impairments. Neuronal death in hippocampal CA1 is thought to be an important mechanism of these impairments. However, it is also possible that functional interactions between surviving neurons are important. In this study we recorded in vivo single-unit activity in the CA1 hippocampal region of rats while they performed a spatial memory task. From these data we constructed functional networks describing pyramidal cell interactions. To build the networks, we used maximum entropy algorithms previously applied only to in vitro data. We show that several months following SE pyramidal neurons display excessive neuronal synchrony and less neuronal reactivation during rest compared with those in healthy controls. Both effects predict rat performance in a spatial memory task. These results provide a physiological mechanism for SE-induced cognitive impairment and highlight the importance of the systems-level perspective in investigating spatial cognition.
Kashouty, Rabih; Yono, Noor; Al Samara, Mershed
Milk-alkali syndrome is mainly caused by the ingestion of large amounts of calcium and absorbable alkali. This syndrome can lead to metastatic calcification, renal failure and metabolic alkalosis secondary to hypercalcemia. Hypercalcemia is rarely a cause of seizure activity. Very few case reports have been published linking seizure to hypercalcemia, but only one recent case report about mesial temporal sclerosis relates the seizure activity to Milk-alkali syndrome. This is another report regarding seizure associated with excess calcium carbonate intake, but without any evidence of mesial temporal sclerosis. The patient described in this article, suffered from status epilepticus most likely secondary to hypercalcemia. Evaluations for malignancy, thyroid, and parathyroid dysfunctions were non conclusive, therefore hypercalcemia in our patient was attributed to milk-alkali syndrome given the history of the prolonged calcium carbonate intake.
Basha, Maysaa M; Alqallaf, Abdulradha; Shah, Aashit K
Refractory status epilepticus (RSE) can lack overt clinical manifestation and is usually treated with continuous infusion of intravenous anesthetic drugs (IVADs), where the use of continuous electroencephalography (cEEG) is imperative. Ketamine has recently been shown to be effective in the treatment of RSE. We retrospectively review a cohort of 11 patients receiving ketamine as part of their treatment regimen for RSE. We report on the presence of a characteristic EEG rhythm consisting of a generalized archiform theta to beta rhythms (7-20 Hz) appearing after ketamine administration. This pattern was seen in five patients, four of whom achieved successful resolution of RSE. Ketamine-induced EEG pattern may serve as a biomarker predictive of successful treatment outcome in RSE. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
Bhaskara Rao, Janapareddy Vijaya; Vengamma, Bhuma; Naveen, Thota; Rao, Marella Sudhakar
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. PMID:24339580
Bhaskara Rao, Janapareddy Vijaya; Vengamma, Bhuma; Naveen, Thota; Rao, Marella Sudhakar
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.
Thill, Chloé; Di Constanzo, Laurence; Pessey, François; Aries, Philippe; Montelescaut, Étienne; Sapin, Jeanne; Vaillant, Catherine; Drouillard, Isabelle
Baclofen is an agonist of peripheral and central B gamma-aminobutyric acid receptors, whose activation causes a myorelaxation and a powerfull depression of the central nervous system. Moreover, it has an action against addiction, in reducing craving. Commercialized since 1975 in France, to control muscle spasticity due to medullar affection or multiple sclerosis, it receives a temporary recommendation of use in march 2014, as a last-line adjuvant treatment in alcohol withdrawal. Beyond its therapeutic use, baclofen is involved in many self-induced intoxications. We report the case of a patient who develops, after a massive ingestion of baclofen (supposed dose ingested: 1 200 mg), a hypotonic and calm coma, requiring her admission in our intensive care unit, and then a status epilepticus.
Novy, Jan; Hubschmid, Monica; Michel, Patrik; Rossetti, Andrea O
Levetiracetam (LEV) has been considered to undergo no significant change in bioavailability during pregnancy; however, it was recently demonstrated to display modifications leading to a drop in its serum level. We describe a patient who displayed impending status epilepticus following a fall in her LEV level during the first trimester. The oral LEV dosage was increased, and phenytoin and benzodiazepines were transiently prescribed. She experienced severe anxiety and an unbearable fear over the deleterious consequences for her baby despite repeated, reassuring explanations. Her anxiety was so strong that she aborted electively shortly after leaving the hospital. This observation emphasizes the need for LEV level monitoring during pregnancy to prevent unexpected seizure relapses. The rapid increase in levetiracetam dosage in parallel with the loss of seizure control is suspected of facilitating the induction of significant psychiatric changes.
Ramanujam, Bhargavi; Arora, Amit; Malhotra, Varun; Dash, Deepa; Mehta, Santosh; Tripathi, Manjari
Catamenial epilepsy (CE) is a commonly observed phenomenon among women with epilepsy, the management of which is both hormonal and non-hormonal. Progesterone therapy has been tried in these patients, as the possible mechanism of CE is withdrawal of progesterone and a higher oestrogen/progesterone ratio in the perimenstrual and periovulatory periods. Here, we describe a 24-year-old lady with multiple seizure types since childhood, which were refractory to adequate antiepileptic drug therapy after menarche with catamenial clustering of seizures. She went on to have several episodes of non-convulsive status epilepticus also with similar periodicity, which would abate only with midazolam infusion, without the need for ventilatory support. She was tried on acetazolamide, progesterone vaginal pessaries, and maximum tolerated doses of antiepileptic medications, but finally responded to intramuscular and oral progesterone, and has been seizure-free for more than a year.
Fujisao, Elaine Keiko; Cristaldo, Nathalia Raquel; da Silva Braga, Aline Marques; Cunha, Paulina Rodrigues; Yamashita, Seizo; Betting, Luiz Eduardo
A 59-year-old man was admitted with respiratory tract infection, compromised conscience and generalized tonic-clonic seizures. His medical history included schizophrenia diagnosis, for which he had been being treated since he was 27 years old. EEG disclosed non-convulsive status epilepticus. A magnetic resonance image (MRI) acquired 3 days later showed increased left hippocampal volume with hyperintensity on T2-weighted and FLAIR sequences. After being treated with antibiotics and antiepileptic medications, the patient's condition improved. A follow-up MRI showed reduction of the left hippocampus. The relationship between epilepsy and schizophrenia is not yet clear. This case illustrates this interaction. Hippocampal atrophy may have been caused by environmental aggression in the present patient with schizophrenia, perhaps in association with a predisposing genotype.
Taylor, Connie; Piantino, Juan; Hageman, Joseph; Lyons, Evelyn; Janies, Kathryn; Leonard, Daniel; Kelley, Kent; Fuchs, Susan
The purpose of this survey and record review was to characterize emergency department management of unprovoked seizures and status epilepticus in children in Illinois. The survey was sent to 119 participating emergency departments in the Emergency Medical Services for Children program; responses were received from 103 (88% response rate). Only 44% of the emergency departments had a documented protocol for seizure management. Only 12% of emergency departments had child neurology consultation available at all times. Record review showed that 58% of patients were discharged home, 26% were transferred to another institution, and 10% were admitted to a non-intensive care unit setting. Ninety percent of patients were treated with anticonvulsants. Seizure education was provided by the primary emergency department nurse (97%) and the treating physician (79%). This project demonstrated strengths and weaknesses in the current management of pediatric seizure patients in Illinois emergency departments. © The Author(s) 2015.
Schuster, Angel Lorrine; Honeycutt, Travis C B; Hamrick, Harvey James
Despite the publication of a number of case reports since the 1950s, physician awareness of the unique relationship between cat scratch disease (CSD) and acute encephalopathy remains limited. This report alerts emergency medicine physicians to include CSD encephalopathy (CSDE) in the differential diagnosis when a previously healthy child presents with status epilepticus. Prompt recognition of this relationship impacts the selection of initial diagnostic studies and antibiotic choices and permits reliable insight into prognosis. The 2 cases are from different eras and demonstrate the significant diagnostic advances in the past 3 decades for Bartonella henselae infection. Both children were treated with antibiotics, and both had resolution of all neurological symptoms. However, the role of antibiotics in the treatment and outcome of CSDE remains speculative. Lastly, the report suggests potential areas of investigation to address immune-mediated mechanisms in the pathogenesis of CSDE.
Guilbert, J; Flamant, C; Hallalel, F; Doummar, D; Frata, A; Renolleau, S
We describe a case of a young child who lived in Hong Kong who presented with a severe epilepticus status after a return flight to Paris. Routine laboratory tests failed to establish a cause. Upon further questioning, the parents reported that the nanny had given an abdominal massage to the child with an unlabelled solution reported to have anti-flatulence effects. Toxicological analysis of this solution revealed the presence of camphor. Although the highly toxic effects of camphor have long been established, the present case illustrates that camphor continues to be a source of paediatric exposure. This case highlights the importance of systematic questioning and recalls the extreme danger associated with camphor even when administered transcutaneously.
Helbok, Raimund; Claassen, Jan
The underlying pathophysiology of status epilepticus (SE) remains mostly invisible to the clinician in the intensive care unit (ICU) setting. In animal studies associated hemodynamic and brain neurochemical changes have been well described. In the last decade, bedside invasive neuromonitoring techniques allow the assessments of changes in focal and global cerebral physiology associated with ictal activity on the tissue level in humans. Recent studies demonstrate that laboratory research insufficiently replicates the complexity of the human condition. Herein we summarize the current knowledge gained from human studies integrating cortical electrographic and brain tissue metabolic and hemodynamic information into the current pathophysiologic concept of SE in humans. With increasing experience gained by the use of extended neuromonitoring, we are more and more able to understand associated hemodynamic and brain neurochemical changes in patients with SE. In the future, this information can potentially provide integrated pathophysiologic end points into SE treatment concepts. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
Liu, Jian Xin; Liu, Yong; Tang, Feng Ru
We investigated the protein expression of different protein kinase C (PKC) isoforms (PKC-alpha, PKC-beta1, PKC-beta2, PKC-gamma, PKC-delta, PKC-epsilon, PKC-eta and PKC-zeta) in the hippocampus of normal control mice and progressive changes in PKC isoforms expression during and after pilocarpine induced status epilepticus (PISE). We showed the reduced expression of PKC-delta, PKC-eta and PKC-zeta in interneurons in the CA1 area and in the hilus of the dentate gyrus during or after PISE. Increased expression of PKC-alpha and PKC-beta1 was demonstrated in the stratum pyramidale of CA3 area, and PKC-epsilon was up-regulated in the stratum lucidum of the CA3 area during or after PISE. Our results suggest that hippocampal PKC isoforms may play different roles in seizure generation, and be targets for development of anti-convulsive drugs.
Fujisao, Elaine Keiko; Cristaldo, Nathalia Raquel; da Silva Braga, Aline Marques; Cunha, Paulina Rodrigues; Yamashita, Seizo; Betting, Luiz Eduardo
A 59-year-old man was admitted with respiratory tract infection, compromised conscience and generalized tonic–clonic seizures. His medical history included schizophrenia diagnosis, for which he had been being treated since he was 27 years old. EEG disclosed non-convulsive status epilepticus. A magnetic resonance image (MRI) acquired 3 days later showed increased left hippocampal volume with hyperintensity on T2-weighted and FLAIR sequences. After being treated with antibiotics and antiepileptic medications, the patient’s condition improved. A follow-up MRI showed reduction of the left hippocampus. The relationship between epilepsy and schizophrenia is not yet clear. This case illustrates this interaction. Hippocampal atrophy may have been caused by environmental aggression in the present patient with schizophrenia, perhaps in association with a predisposing genotype. PMID:28220103
Yoshii, Akira; Takeoka, Masanori; Kelly, Peter J; Krishnamoorthy, Kalpahty S
Pyridoxine-dependent epilepsy usually presents in the neonatal period or even in utero, is refractory to antiepileptic medications, and is treatable with lifelong administration of pyridoxine. The seizures are typically generalized tonic-clonic, although myoclonic seizures or infantile spasms have been described. We report an infant who presented at 5 months of age with a right-sided clonic seizure with fever. Subsequently, she had recurrent right focal or generalized seizures despite sequential treatment with various antiepileptic medications. At 7 months, she was hospitalized with status epilepticus, which was finally controlled with pyridoxine. After she became seizure free, she continued to have a strong left arm preference with mild weakness of the right arm and delayed language skill. Eventually, she outgrew these symptoms. This case illustrates that pyridoxine-dependent epilepsy, although rare, must be included in the differential diagnosis of focal seizures, especially when the seizures are refractory to traditional antiepileptic drugs.
Patten, William; Naqvi, Sayed Z; Raszynski, Andre; Totapally, Balagangadhar R
The objective of this retrospective study was to evaluate complications in the management of refractory status epilepticus (RSE) treated with benzodiazepine and pentobarbital infusions. Of 28 children with RSE, eleven (39%) were treated with a pentobarbital infusion after failure to control RSE with a benzodiazepine infusion; while17 children (61%) required only a benzodiazepine infusion. The mean maximum pentobarbital infusion dosage was 5.2 ± 1.8 mg/kg/h. Twenty-five patients received a continuous midazolam infusion with an average dosage of 0.41 ± 0.43 mg/kg/h. The median length of stay was longer for the pentobarbital group. Children requiring pentobarbital therapy were more likely to develop hypotension, require inotropic support, need intubation, mechanical ventilation, peripheral nutrition, and blood products; furthermore, they were more likely to develop hypertension and movement disorder after or during weaning. In conclusion, children with RSE who required pentobarbital therapy had a longer hospital stay with more complications.
Lingappa, Lokesh; Konanki, Ramesh; Patel, Ravi; Vooturi, Sudhindra; Jayalakshmi, Sita
The current study evaluates the etiology, clinical course and outcome of refractory convulsive status epilepticus (CSE) in older children. Retrospective analysis of data of 73 children with CSE, aged ≥2 and ≤12 years was performed. Odds ratios were calculated between variables for clinical course and outcome. Mortality of the group was analyzed using survival analysis. Thirty three (45.2%) children progressed to refractory status epilepticus (RSE). The most common etiology for CSE was acute symptomatic in 44 (60.3%) of which 37 had presumed CNS infections. The odds of progressing to RSE were higher in children with acute symptomatic etiology (OR 2.62; CI - 95%; 0.99-7.14; p=0.041). Progression to RSE increased the chances of severe sepsis by six times (OR 6.08; CI - 95%; 1.19-31.02; p=0.036) and acidosis by nearly 15 times (OR 14.77; CI - 95%; 1.19-31.02; p=0.020). Overall mortality was 13.7%, higher in RSE (21.2% vs.7.5%). Amongst the 63 surviving children followed for 1 year from discharge, progression to RSE increased the odds of disability by seven times (OR 7.08; CI 29.31; p=0.004). Acute symptomatic etiology was the commonest cause of CSE among older children from developing country and increased the odds of progressing to RSE. RSE was significantly associated with disability at 1 year from discharge. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Misra, Usha K; Kalita, Jayantee; Bhoi, Sanjeev K; Dubey, Deepanshu
Status epilepticus (SE) is one of the most important neurological emergencies. The present study evaluated both direct cost of SE and predictors of cost in an Indian tertiary care teaching hospital in Lucknow India. SE was defined as continuous seizure for ≥ 5 min or recurrent seizures without regaining consciousness. Etiologies of SE were categorized as acute central nervous system (CNS) pathology, acute non-CNS pathology, chronic CNS pathology, congenital disorders and others. Patients requiring mechanical ventilation (MV) received ventilators free of cost. Mortality and disability on discharge were noted. Fifty-five patients aged 8-90 years were included (males, 33). Fifty (89.3%) patients had generalized convulsive SE. The severity of SE as assessed by Status Epilepticus Scoring Scale was unfavorable (score, 3-6) in 41 (74.5%) patients. The etiology of SE was categorized as acute CNS pathology in 28 (51%) patients, non-CNS and chronic CNS pathology in 11 (19.6%) patients each, remote congenital pathology in 2 (3.6%), and others in 3 (5.6%). Thirty (53.6%) patients had comorbidities. Median duration of hospitalization was 7 (range, 1-72) days.Twenty six patients were hospitalized for >7 days. SE was controlled by 2 drugs in 47 (85.5%) patients and refractory to 2 intravenous antiepileptic drugs in 8 (14.5%). Nineteen (34.5%) patients died, and 29 (51.8%) showed favorable outcomes on discharge. Median hospital expenditure per case was INR 19,900 ($309.87; range, INR 1600-574,000). On multivariate analysis, SE hospitalization costs were determined by refractoriness of SE and mechanical ventilation (MV). Hospitalization cost of SE was lower than those of stroke. Acute non-CNS pathology is largely responsible for the high cost of SE, particularly refractory SE requiring mechanical ventilation. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Alvarez, Vincent; Drislane, Frank W.; Westover, M. Brandon; Dworetzky, Barbara A.; Lee, Jong Woo
Summary Objective Continuous electroencephalography (cEEG) is important for treatment guidance in status epilepticus (SE) management, but its role in clinical outcome prediction is unclear. Our aim is to determine which cEEG features give independent outcome information after correction for clinical predictor. Methods cEEG data of 120 consecutive adult patients with SE were prospectively collected in three academic medical centers using the 2012 American Clinical Neurophysiology Society’s Standardized Critical Care EEG Terminology. Association between cEEG features and two clinical outcome measures (mortality and complete recovery) was assessed. Results In the first 24 h of EEG recording, 49 patients (40.8%) showed no periodic or rhythmic pattern, 45 (37.5%) had periodic discharges, 20 (16.7%) had rhythmic delta activity, and 6 (5%) had spike-and-wave discharges. Seizures were recorded in 68.3% of patients. After adjusting for known clinical predictive factors for mortality including the STatus Epilepticus Severity Score (STESS) and the presence of a potentially fatal etiology, the only EEG features (among rhythmic and periodic patterns, seizures, and background activity) that remained significantly associated with outcome were the absence of a posterior dominant rhythm (odds ratio [OR] 9.8; p = 0.033) for mortality and changes in stage II sleep pattern characteristics (OR 2.59 for each step up among these categories: absent, present and abnormal, present and normal; p = 0.002) for complete recovery. Significance After adjustment for relevant clinical findings, including SE severity and etiology, cEEG background information (posterior dominant rhythm and sleep patterns) is more predictive for clinical outcome after SE than are rhythmic and periodic patterns or seizures. PMID:25953195
Ilvento, Lucrezia; Rosati, Anna; Marini, Carla; L'Erario, Manuela; Mirabile, Lorenzo; Guerrini, Renzo
The purpose of this study was to report on the efficacy and safety of intravenous ketamine (KE) in refractory convulsive status epilepticus (RCSE) in children and highlight its advantages with particular reference to avoiding endotracheal intubation. Since November 2009, we have used a protocol to treat RCSE including intravenous KE in all patients referred to the Neurology Unit of the Meyer Children's Hospital. From November 2009 to February 2015, 13 children (7 females; age: 2 months-11 years and 5 months) received KE. Eight patients were treated once, two were treated twice, and the remaining three were treated 3 times during different RCSE episodes, for a total of 19 treatments. Most of the RCSE episodes were generalized (14/19). A malformation of cortical development was the most frequent etiology (4/13 children). Ketamine was administered from a minimum of 22 h to a maximum of 17 days, at doses ranging from 7 to 60 mcg/kg/min, obtaining a resolution of the RCSE in 14/19 episodes. Five patients received KE in lieu of conventional anesthetics, thus, avoiding endotracheal intubation. Ketamine was effective in 4 of them. Suppression-burst pattern was observed after the initial bolus of 3mg/kg in the majority of the responder RCSE episodes (10/14). Ketamine is effective in treating RCSE and represents a practical alternative to conventional anesthetics for the treatment of RCSE. Its use avoids the pitfalls and dangers of endotracheal intubation, which is known to worsen RCSE prognosis. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.
Kaminski, Rafal M.; Fu, Zhanyan; Venkatesan, Kumar; Mazzuferi, Manuela; Leclercq, Karine; Seutin, Vincent; Vicini, Stefano
Systemic injection of high doses of 11-deoxycortisol succinate had been reported to induce status epilepticus in rats and cats that was associated with paroxysmal epileptiform activity refractory to first generation antiepileptic drugs (AEDs). Using patch-clamp recordings we have investigated the mechanisms of 11-deoxycortisol-induced excitability and we have discovered that this molecule accelerates the decay time of the inhibitory postsynaptic currents (IPSCs) mediated by GABAA receptors, both in neuronal cultures and in hippocampal slices. In addition, it reduces the amplitude and frequency of IPSCs. Thus, 11-deoxycortisol action on GABAergic neurotransmission may be one of the underlying causes of convulsive seizures that had been observed in rats. In the present study, we have reproduced the ability of 11-deoxycortisol to induce convulsive seizures after intravenous infusion in mice. The threshold dose of 11-deoxycortisol necessary for seizure induction was also determined (0.95 mmol/kg). Furthermore, we have established that these seizures are completely refractory to several AEDs such as phenytoin (up to 100 mg/kg), carbamazepine (up to 56 mg/kg), and valproate (up to 300 mg/kg). Levetiracetam and diazepam afforded only limited protection at high doses, 540 and 3–10 mg/kg, respectively. Interestingly, long-lasting seizures induced by 11-deoxycortisol in mice were not associated with typical neuropathological changes observed in other models of status epilepticus. We propose that 11-deoxycortisol-induced seizures may be an advantageous experimental model of drug-resistant epilepsy. Finally, better understanding of the pro-epileptic properties of 11-deoxycortisol is very important, because this endogenous steroid precursor may play a role in the pathophysiology of epilepsy. PMID:20883706
Read, M I; Harrison, J C; Kerr, D S; Sammut, I A
Background and Purpose Status epilepticus is increasingly associated with cardiac injury in both clinical and animal studies. The current study examined ECG activity for up to 48 h following kainic acid (KA) seizure induction and compared the potential of atenolol and clonidine to attenuate this cardiac pathology. Experimental Approach Sprague-Dawley rats (male, 300–350 g) were implanted with ECG and electrocorticogram electrodes to allow simultaneous telemetric recordings of cardiac and cortical responses during and after KA-induced seizures. Animals were randomized into saline controls, and saline vehicle-, clonidine- or atenolol-pretreated KA groups. Key Results KA administration in the saline-pretreated group produced an immediate bradycardic response (maximal decrease of 28 ± 6%), coinciding with low-level seizure activity. As high-level seizure behaviours and EEG spiking increased, tachycardia also developed, with a maximum heart rate increase of 38 ± 7% coinciding with QTc prolongation and T wave elevation. Both clonidine and atenolol pretreatment attenuated seizure activity and reduced KA-induced changes in heart rate, QTc interval and T wave amplitude observed during both bradycardic and tachycardic phases in saline-pretreated KA animals. Clonidine, however, failed to reduce the power of EEG frequencies. Atenolol and to a lesser extent clonidine attenuated the cardiac hypercontraction band necrosis, inflammatory infiltration, and oedema at 48 h after KA, relative to the saline-KA group. Conclusions and Implications Severe seizure activity in this model was clearly associated with altered ECG activity and cardiac pathology. We suggest that modulation of sympathetic activity by atenolol provides a promising cardioprotective approach in status epilepticus. PMID:25765931
Mazurkiewicz-Bełdzińska, Maria; Szmuda, Marta; Zawadzka, Marta; Matheisel, Agnieszka
The management of status epilepticus (SE) has changed in recent years. Substantial differences exist regarding the definition and time frame of a seizure, which has been operationally defined as lasting for 5 min. Not only have many new intravenous drugs, such as levetiracetam and lacosamide been introduced but other routes of administration, such as intranasal or buccal administration for midazolam, are also being developed. Optimal and successful therapy initiated at the appropriate moment, adequately tailored to the clinical state of the patient, determines the first step in the normalisation of vital functions and leads to the restoration of the physiological homeostatic mechanisms of the organism. The aim of this review is to present the current treatment options for the management of convulsive status epilepticus (CSE) that have been widely confirmed as the most effective in clinical trials and approved by the international neurology authorities as the actual therapeutic standards. We also intend to indicate distinct and unequivocal differentiation and therapeutic indications for each phase of CSE, including the precise doses of the related medications, to present practical guidelines for clinicians. The treatment of patients with CSE requires emergency physicians, neurologists and specialists in intensive care to work together to provide optimal care that should be initiated as soon as possible and conducted as a unified procedure to improve neurocritical care in patients who are transferred from the ambulance service, through the emergency department and finally to the neurology department or ICU. Appropriate treatment also involves avoiding mistakes associated with inadequate doses of medications, overdosing a patient or choosing an inappropriate medication.
Sánchez Fernández, Iván; Abend, Nicholas S; Arndt, Daniel H; Carpenter, Jessica L; Chapman, Kevin E; Cornett, Karen M; Dlugos, Dennis J; Gallentine, William B; Giza, Christopher C; Goldstein, Joshua L; Hahn, Cecil D; Lerner, Jason T; Matsumoto, Joyce H; McBain, Kristin; Nash, Kendall B; Payne, Eric; Sánchez, Sarah M; Williams, Korwyn; Loddenkemper, Tobias
To describe the prevalence, characteristics, and predictors of electrographic seizures after convulsive status epilepticus (CSE). This was a multicenter retrospective study in which we describe clinical and electroencephalographic (EEG) features of children (1 month to 21 years) with CSE who underwent continuous EEG monitoring. Ninety-eight children (53 males) with CSE (median age of 5 years) underwent subsequent continuous EEG monitoring after CSE. Electrographic seizures (with or without clinical correlate) were identified in 32 subjects (33%). Eleven subjects (34.4%) had electrographic-only seizures, 17 subjects (53.1%) had electroclinical seizures, and 4 subjects (12.5%) had an unknown clinical correlate. Of the 32 subjects with electrographic seizures, 15 subjects (46.9%) had electrographic status epilepticus. Factors associated with the occurrence of electrographic seizures after CSE were a previous diagnosis of epilepsy (P = .029) and the presence of interictal epileptiform discharges (P < .0005). The median (p25-p75) duration of stay in the pediatric intensive care unit was longer for children with electrographic seizures than for children without electrographic seizures (9.5 [3-22.5] vs 2 [2-5] days, Wilcoxon test, Z = 3.916, P = .0001). Four children (4.1%) died before leaving the hospital, and we could not identify a relationship between death and the presence or absence of electrographic seizures. After CSE, one-third of children who underwent EEG monitoring experienced electrographic seizures, and among these, one-third experienced entirely electrographic-only seizures. A previous diagnosis of epilepsy and the presence of interictal epileptiform discharges were risk factors for electrographic seizures. Copyright © 2014 Mosby, Inc. All rights reserved.
Fernández, Iván Sánchez; Abend, Nicholas S.; Arndt, Daniel H.; Carpenter, Jessica L.; Chapman, Kevin E; Cornett, Karen M.; Dlugos, Dennis J.; Gallentine, William B.; Giza, Christopher C; Goldstein, Joshua L; Hahn, Cecil D; Lerner, Jason T; Matsumoto, Joyce H; McBain, Kristin; Nash, Kendall B; Payne, Eric; Sánchez, Sarah M; Williams, Korwyn; Loddenkemper, Tobias
Objectives To describe the prevalence, characteristics and predictors of electrographic seizures following convulsive status epilepticus (CSE). Study design Multicenter retrospective study describing clinical and electroencephalographic (EEG) features of children (1 month-21 years) with CSE who underwent continuous EEG monitoring. Results Ninety-eight children (53 males) with a median age of 5 years with CSE underwent subsequent continuous EEG monitoring after CSE. Electrographic seizures (with or without clinical correlate) were identified in 32 subjects (33%). Eleven subjects (34.4%) had electrographic-only seizures, 17 subjects (53.1%) had electro-clinical seizures, and 4 subjects (12.5%) had an unknown clinical correlate. Of the 32 subjects with electrographic seizures, 15 subjects (46.9%) had electrographic status epilepticus. Factors associated with the occurrence of electrographic seizures after CSE were a prior diagnosis of epilepsy (p= 0.029) and the presence of interictal epileptiform discharges (p< 0.0005). The median (p25–p75) duration of stay in the pediatric intensive care unit was longer for children with electrographic seizures than for children without electrographic seizures [9.5 (3–22.5) versus 2 (2–5) days, Wilcoxon test, Z=3.916, p=0.0001]. Four children (4.1%) died before leaving the hospital and we could not identify a relationship between death and the presence or absence of electrographic seizures. Conclusions Following CSE, one-third of children who underwent EEG monitoring experienced electrographic seizures, and among these, one-third experienced entirely electrographic-only seizures. A prior diagnosis of epilepsy and the presence of interictal epileptiform discharges were risk factors for electrographic seizures. PMID:24161223
Wilkes, Ryan; Tasker, Robert C
A systematic literature search and review of the best evidence for intensive care treatment of refractory status epilepticus in children using continuous infusion of midazolam or anesthetic agents. MEDLINE and EMBASE search before December 2013 using key words and/or Medical Subject Headings identified English-language citations that were screened for eligibility and used if 1) the study was about high-dose benzodiazepine or anesthetic agent for children; 2) the treatment protocol was described and used for refractory status epilepticus; 3) the outcomes included seizure control; and 4) the series included at least five children. Sixteen studies (645 patients) were identified, including midazolam (nine studies), barbiturate (four studies), and other anesthetic approaches (three studies). When midazolam was used as the initial agent for refractory status epilepticus, the rate of clinical seizure control was 76%, which was achieved on average 41 minutes after starting the infusion. When midazolam was used in conjunction with continuous electroencephalography, the time to seizure control was much longer and the mean dose required for seizure control was 10.7 μg/kg/min compared with a lower dose (2.8 μg/kg/min) in the studies not using this form of monitoring, suggesting that continuous electroencephalography provided additional targets for treatment. Barbiturates were usually used after midazolam failed and treatment was started, on average, 66 hours after refractory status epilepticus onset with the goal of electroencephalography burst suppression, which was achieved, on average, 22.6 hours later. Among patients failing midazolam, barbiturate infusion was effective in 65%. Inhaled anesthetics, ketamine, and hypothermia were generally used after prior therapy with midazolam and barbiturates had failed, usually several days after seizure onset. The data on intensive care treatment of pediatric refractory status epilepticus are of poor quality, yet they show a
Kaplan, Peter W; Stagg, Ryan
Stuttering is a repetitive, iterative disfluency of speech, and is usually seen as a developmental problem in childhood. Acquired causes in adults include strokes and medications. When stuttering occurs with seizure-like events, it is usually attributed to psychogenic nonepileptic seizures. We describe an elderly man who experienced personality change and bouts of stuttering, followed by anarthria with preserved writing and then aphasia affecting written and uttered language, and ending with confusion. EEG recordings showed nonconvulsive status epilepticus (NCSE) with focality in the left frontal region followed by bifrontal NCSE. This case enlarges our understanding of the behavioral correlates of focal frontal seizures to include simple partial seizures with speech and then language output disturbances (aphemia, then aphasia), progressing to complex partial phenomenology in the setting of frontal NCSE.
Gosavi, Tushar Divakar; See, Siew Ju; Lim, Shih Hui
Electroencephalography findings in nonconvulsive or subtle convulsive status epilepticus (NCSE and SCSE, respectively) can be heterogenous. We aimed to study the different patterns on EEG in our cohort of patients. Our objective was to study ictal and interictal EEG patterns in patients with NCSE and SCSE. From January 2012 to December 2013, EEGs recorded from patients admitted for altered mental status suspected of having NCSE or SCSE were reviewed retrospectively. Electroencephalography status was defined as having (a) continuous ictal discharges lasting >5 min or (b) >2 discrete bursts of ictal discharges, each lasting <5 min, without returning to previous background rhythm in between these bursts. Among 1698 EEGs recorded for at least 30 min from hospitalized patients, 55 (3.23%) satisfied the criteria of EEG SE. The ictal onset was regional in 37 (67.2%) EEGs, multiregional independent in 8 (14.5%), and generalized in 10 (18.4%). The EEG seizure duration was >5 min in 24 (43.6%) EEGs, between 1 and 5 min in 14 (25.4%), and less than 1 min in 17 (30.8%). Twenty (36.3%) EEGs showed one continuous prolonged seizure episode of >5-minute duration, 15 (27.2%) had 10 or less discrete episodes, 20 (36.3%) had more than 10 episodes, and 11 (20%) had 2 or more ictal patterns. Thirty (54.5%) EEGs had onset ictal frequency of >8 Hz whereas the rest had <8-Hz ictal frequency. In the interictal segment, 29 patients had continuous generalized slow waves, while 12 had intermittent generalized slow waves. Eleven patients had continuous slow waves lateralized to one hemisphere, and these were ipsilateral to the ictal focus in 10 but contralateral in 1. Other interictal waves seen were PLEDS (6), sharp waves (3), suppression (5), and triphasic waves (1). The background alpha rhythm was absent in 36 patients and slow in 14, and normal background alpha was seen in the interictal period in 5 patients. The ictal and interictal EEG patterns in NCSE and SCSE can be varied. Further
Engel, T; Tanaka, K; Jimenez-Mateos, E M; Caballero-Caballero, A; Prehn, J H M; Henshall, D C
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. Analysis of electroencephalogram (EEG) recordings during status epilepticus induced by intra-amygdala kainic acid (KA) showed that seizures lasted significantly longer in p53-deficient mice compared with wild-type animals. Nevertheless, neuronal death in the hippocampal CA3 subfield and the neocortex was significantly reduced at 72 h in p53-deficient mice. Long-term continuous EEG telemetry recordings after status epilepticus determined that the sum duration of spontaneous seizures was significantly longer in p53-deficient compared with wild-type mice. Hippocampal damage and neuropeptide Y distribution at the end of chronic recordings was found to be similar between p53-deficient and wild-type mice. The present study identifies protracted KA-induced electrographic status as a novel outcome of p53 deficiency and shows that the absence of p53 leads to an exacerbated epileptic phenotype. Accordingly, targeting p53 to protect against status epilepticus or related neurologic insults may be offset by deleterious consequences of reduced p53 function during epileptogenesis or in chronic epilepsy. PMID:21368852
Spagnoli, Carlotta; Cilio, Maria Roberta; Pavlidis, Elena; Pisani, Francesco
Neonatal seizures have been associated with the later development of postneonatal epilepsy, mainly beginning within the first year of life. Mechanisms of epileptogenesis in the immature brain still need to be fully elucidated but a two-hit hypothesis, showing that an early insult heightens later susceptibility to seizure-induced brain damage, has been demonstrated in animal models. We describe 2 cases of preterm babies sustaining recurrent neonatal seizures in the context of a severe perinatal brain damage who presented with symptomatic epilepsy only after the occurrence of an episode of febrile status epilepticus. In the context of preexisting perinatal brain damage, febrile status epilepticus acted as a second hit for developing epilepsy, confirming animal evidence. © The Author(s) 2014.
Accardo, Jennifer; De Lisi, Domenico; Lazzerini, Paola; Primavera, Alberto
In anoxic coma, myoclonic status epilepticus and other nonreactive epileptiform patterns are considered as signs of poor prognosis. We report the case of a good recovery in a prolonged comatose myoclonic status epilepticus (MSE) after a cardiac arrest (CA) treated with mild therapeutic hypothermia (TH) in a patient who had undergone a bone marrow transplantation for Hodgkin's lymphoma. This case emphasizes the opportunity of performing an electroencephalogram (EEG) in the acute period after an hypoxic-ischemic insult and underlines the diagnostic difficulties between MSE and Lance-Adams syndrome, which classically occurs after the patient has regained consciousness, but can also begin while the patient is still comatose or sedated. Major problems in prognostication for postarrest comatose patients will also be pointed out.
Höfler, Julia; Rohracher, Alexandra; Kalss, Gudrun; Zimmermann, Georg; Dobesberger, Judith; Pilz, Georg; Leitinger, Markus; Kuchukhidze, Giorgi; Butz, Kevin; Taylor, Alexandra; Novak, Helmut; Trinka, Eugen
The aim was to describe the safety and efficacy of (S)-ketamine [(S)-KET] in a series of patients with refractory and super-refractory status epilepticus (RSE and SRSE) in a specialized neurological intensive care unit (NICU). We retrospectively analyzed the data of patients with RSE and SRSE treated with (S)-KET in the NICU, Salzburg, Austria, from 2011 to 2015. Data collection included demographic features, clinical presentation, diagnosis, electroencephalogram (EEG) data, anticonvulsant treatment, timing, and duration of treatment with (S)-KET. Outcomes were seizure control and death. A total of 42 patients (14 women) with RSE and SRSE were treated with (S)-KET. The median duration of status epilepticus (SE) was 10 days [first quartile (Q1) 5.0, Q3 21.0]; the median latency from SE onset to the first administration of (S)-KET was 3 days (Q1 2.0, Q3 6.8). Prior to (S)-KET administration, patients had received a median of two (Q1 2.0, Q3 3.0) anesthetics and three (Q1 2.0, Q3 4.0) antiepileptic drugs. Forty percent of patients (17/42) received propofol: 65 % prior to (S)-KET; 35 % at the same time with (S)-KET. Seven patients received a median bolus of (S)-KET of 200 mg (Q1 200, Q3 250) followed by a continuous infusion, while 35 started with a continuous infusion (maximum rate median 2.55 mg/kg/h; Q1 2.09, Q3 3.22). In 64 % of patients (27/42), (S)-KET was the last drug before SE cessation; in five patients, it was given with propofol at the same time. Median duration of administration was 4 days (Q1 2.0, Q3 6.8). Overall (S)-KET treatment was well tolerated, adverse effects were not observed, and overall mortality was 45.2 %. Treatment of SRSE in adult patients with (S)-KET led to resolution of status in 64 %. No adverse events were found, indicating a favorable safety profile.
Vooturi, Sudhindra; Jayalakshmi, Sita; Sahu, Sambit; Mohandas, Surath
To evaluate the etiological profile, clinical characteristics and outcome of patients with refractory generalized convulsive status epilepticus treated in Neurological Intensive Care Unit (NICU). In this open cohort study, data of 126 patients, aged 18 years and above, with convulsive status epilepticus (SE) admitted in NICU was collected. Status epilepticus was defined as seizures lasting for more than five minutes without regaining consciousness. Refractory SE (RSE) was defined as SE refractory to 2 antiepileptic drugs and requiring anesthetic agents for seizure control. Survival and regression analysis were done to analyze the outcome and factors predicting outcome respectively in the study population. Out of 126 patients, 81 patients had non -refractory status epilepticus (NRSE); 45 (35.7%) had RSE. Acute symptomatic etiology was noted in 58.6% of entire cohort. Significantly higher percentage of patients with RSE had an etiology of CNS infections than NRSE group (44.4% vs. 23.5%; P=0.0171). Amongst the CNS infections, viral encephalitis was significantly higher in RSE than NRSE patients (31% vs. 6.2%; P=0.0004). All the patients with RSE required mechanical ventilation. Overall mortality was 19%. The mortality in RSE was 42% (19 out of 45), significantly higher when compared to NRSE where only 6% (5 out of 81) died. On logistic regression, the only predictor of death was fever with an odds ratio of 8.55 (P=0.024). CNS infections, especially viral encephalitis and complications of mechanical ventilation were significantly higher in adult RSE patients. Although mortality is higher in adult patients with RSE, etiology does not contribute to mortality; however fever predicts mortality in these patients. Aggressive management of underlying etiology and prevention of systemic complications may improve outcome in adult RSE patients. Copyright © 2014 Elsevier B.V. All rights reserved.
Jimenez-Mateos, Eva M.; Bray, Isabella; Sanz-Rodriguez, Amaya; Engel, Tobias; McKiernan, Ross C.; Mouri, Genshin; Tanaka, Katsuhiro; Sano, Takanori; Saugstad, Julie A.; Simon, Roger P.; Stallings, Raymond L.; Henshall, David C.
When an otherwise harmful insult to the brain is preceded by a brief, noninjurious stimulus, the brain becomes tolerant, and the resulting damage is reduced. Epileptic tolerance develops when brief seizures precede an episode of prolonged seizures (status epilepticus). MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators of gene expression. We investigated how prior seizure preconditioning affects the miRNA response to status epilepticus evoked by intra-amygdalar kainic acid in mice. The miRNA was extracted from the ipsilateral CA3 subfield 24 hours after focal-onset status epilepticus in animals that had previously received either seizure preconditioning (tolerance) or no preconditioning (injury), and mature miRNA levels were measured using TaqMan low-density arrays. Expression of 21 miRNAs was increased, relative to control, after status epilepticus alone, and expression of 12 miRNAs was decreased. Increased miR-132 levels were matched with increased binding to Argonaute-2, a constituent of the RNA-induced silencing complex. In tolerant animals, expression responses of >40% of the injury-group-detected miRNAs differed, being either unchanged relative to control or down-regulated, and this included miR-132. In vivo microinjection of locked nucleic acid-modified oligonucleotides (antagomirs) against miR-132 depleted hippocampal miR-132 levels and reduced seizure-induced neuronal death. Thus, our data strongly suggest that miRNAs are important regulators of seizure-induced neuronal death. PMID:21945804
Sakurai, Masashi; Kurokawa, Haruna; Shimada, Akinori; Nakamura, Kazuhiro; Miyata, Hajime; Morita, Takehito
Recurrent seizures without interictal resumption (status epilepticus) have been reported to induce neuronal death in the midline thalamic region that has functional roles in memory and decision-making; however, the pathogenesis underlying status epilepticus-induced thalamic neuronal death is yet to be determined. We performed histological and immunohistochemical studies as well as cerebral blood flow measurement using 4.7 tesla magnetic resonance imaging spectrometer on midline thalamic region in Sprague-Dawley rats (n = 75, male, 7 weeks after birth, body weight 250-300 g) treated with intraperitoneal injection of kainic acid (10 mg/kg) to induce status epilepticus (n = 55) or normal saline solution (n = 20). Histological study using paraffin-embedded specimens revealed neuronal death showing ischemic-like changes and Fluoro-Jade C positivity with calcium deposition in the midline thalamic region of epileptic rats. The distribution of neuronal death was associated with focal loss of immunoreactivity for excitatory amino acid transporter 2 (EAAT2), stronger immunoreaction for glutamate and increase in number of Iba-1-positive microglial cells showing swollen cytoplasm and long processes. Double immunofluorescence study demonstrated co-expression of interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) within microglial cells, and loss of EAAT2 immunoreactivity in reactive astrocytes. These microglial alterations and astrocytic EAAT2 downregulation were also observed in tissue without obvious neuronal death in kainic acid-treated rats. These results suggest the possible role of glutamate excitotoxicity in neuronal death in the midline thalamic region following kainic acid-induced status epilepticus due to astrocytic EAAT2 downregulation following microglial activation showing upregulation of IL-1β and iNOS. © 2014 Japanese Society of Neuropathology.
van Vliet, Erwin A; Otte, Willem M; Wadman, Wytse J; Aronica, Eleonora; Kooij, Gijs; de Vries, Helga E; Dijkhuizen, Rick M; Gorter, Jan A
The mammalian target of rapamycin (mTOR) pathway has received increasing attention as a potential antiepileptogenic target. Treatment with the mTOR inhibitor rapamycin after status epilepticus reduces the development of epilepsy in a rat model. To study whether rapamycin mediates this effect via restoration of blood-brain barrier (BBB) dysfunction, contrast-enhanced magnetic resonance imaging (CE-MRI) was used to determine BBB permeability throughout epileptogenesis. Imaging was repeatedly performed until 6 weeks after kainic acid-induced status epilepticus in rapamycin (6 mg/kg for 6 weeks starting 4 h after SE) and vehicle-treated rats, using gadobutrol as contrast agent. Seizures were detected using video monitoring in the week following the last imaging session. Gadobutrol leakage was widespread and extensive in both rapamycin and vehicle-treated epileptic rats during the acute phase, with the piriform cortex and amygdala as the most affected regions. Gadobutrol leakage was higher in rapamycin-treated rats 4 and 8 days after status epilepticus compared to vehicle-treated rats. However, during the chronic epileptic phase, gadobutrol leakage was lower in rapamycin-treated epileptic rats along with a decreased seizure frequency. This was confirmed by local fluorescein staining in the brains of the same rats. Total brain volume was reduced by this rapamycin treatment regimen. The initial slow recovery of BBB function in rapamycin-treated epileptic rats indicates that rapamycin does not reduce seizure activity by a gradual recovery of BBB integrity. The reduced BBB leakage during the chronic phase, however, could contribute to the decreased seizure frequency in post-status epilepticus rats treated with rapamycin. Furthermore, the data show that CE-MRI (using step-down infusion with gadobutrol) can be used as biomarker for monitoring the effect of drug therapy in rats. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
Kortland, Lena-Marie; Alfter, Anne; Bähr, Oliver; Carl, Barbara; Dodel, Richard; Freiman, Thomas M; Hubert, Kristina; Jahnke, Kolja; Knake, Susanne; von Podewils, Felix; Reese, Jens-Peter; Runge, Uwe; Senft, Christian; Steinmetz, Helmuth; Rosenow, Felix; Strzelczyk, Adam
To provide first data on inpatient costs and cost-driving factors due to nonrefractory status epilepticus (NSE), refractory status epilepticus (RSE), and super-refractory status epilepticus (SRSE). In 2013 and 2014, all adult patients treated due to status epilepticus (SE) at the university hospitals in Frankfurt, Greifswald, and Marburg were analyzed for healthcare utilization. We evaluated 341 admissions in 316 patients (65.7 ± [standard deviation]18.2 years; 135 male) treated for SE. Mean costs of hospital treatment were €14,946 (median €5,278, range €776-€152,911, €787 per treatment day) per patient per admission, with a mean length of stay (LOS) of 19.0 days (median 14.0, range 1-118). Course of SE had a significant impact on mean costs, with €8,314 in NSE (n = 137, median €4,597, €687 per treatment day, 22.3% of total inpatient costs due to SE), €13,399 in RSE (n = 171, median €7,203, €638/day, 45.0% of total costs, p < 0.001), and €50,488 in SRSE (n = 33, median €46,223, €1,365/day, 32.7% of total costs, p < 0.001). Independent cost-driving factors were SRSE, ventilation, and LOS of >14 days. Overall mortality at discharge was 14.4% and significantly higher in RSE/SRSE (20.1%) than in NSE (5.8%). Acute treatment of SE, and particularly SRSE and ventilation, are associated with high hospital costs and prolonged LOS. Extrapolation to the whole of Germany indicates that SE causes hospital costs of >€200 million per year. Along with the demographic change, incidence of SE will increase and costs for hospital treatment and sequelae of SE will rise. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.
Rojas, Asheebo; Gueorguieva, Paoula; Lelutiu, Nadia; Quan, Yi; Shaw, Renee; Dingledine, Raymond
Prostaglandin E2 (PGE2) regulates membrane excitability, synaptic transmission, plasticity, and neuronal survival. The consequences of PGE2 release following seizures has been the subject of much study. Here we demonstrate that the prostaglandin E2 receptor 1 (EP1, or Ptger1) modulates native kainate receptors, a family of ionotropic glutamate receptors widely expressed throughout the central nervous system. Global ablation of the EP1 gene in mice (EP1-KO) had no effect on seizure threshold after kainate injection but reduced the likelihood to enter status epilepticus. EP1-KO mice that did experience typical status epilepticus had reduced hippocampal neurodegeneration and a blunted inflammatory response. Further studies with native prostanoid and kainate receptors in cultured cortical neurons, as well as with recombinant prostanoid and kainate receptors expressed in Xenopus oocytes, demonstrated that EP1 receptor activation potentiates heteromeric but not homomeric kainate receptors via a second messenger cascade involving phospholipase C, calcium and protein kinase C. Three critical GluK5 C-terminal serines underlie the potentiation of the GluK2/GluK5 receptor by EP1 activation. Taken together, these results indicate that EP1 receptor activation during seizures, through a protein kinase C pathway, increases the probability of kainic acid induced status epilepticus, and independently promotes hippocampal neurodegeneration and a broad inflammatory response. PMID:24952362
Shinnar, Shlomo; Gloss, David; Alldredge, Brian; Arya, Ravindra; Bainbridge, Jacquelyn; Bare, Mary; Bleck, Thomas; Dodson, W. Edwin; Garrity, Lisa; Jagoda, Andy; Lowenstein, Daniel; Pellock, John; Riviello, James; Sloan, Edward; Treiman, David M.
CONTEXT: The optimal pharmacologic treatment for early convulsive status epilepticus is unclear. OBJECTIVE: To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm. DATA SOURCES: Structured literature review using MEDLINE, Embase, Current Contents, and Cochrane library supplemented with article reference lists. STUDY SELECTION: Randomized controlled trials of anticonvulsant treatment for seizures lasting longer than 5 minutes. DATA EXTRACTION: Individual studies were rated using predefined criteria and these results were used to form recommendations, conclusions, and an evidence-based treatment algorithm. RESULTS: A total of 38 randomized controlled trials were identified, rated and contributed to the assessment. Only four trials were considered to have class I evidence of efficacy. Two studies were rated as class II and the remaining 32 were judged to have class III evidence. In adults with convulsive status epilepticus, intramuscular midazolam, intravenous lorazepam, intravenous diazepam and intravenous phenobarbital are established as efficacious as initial therapy (Level A). Intramuscular midazolam has superior effectiveness compared to intravenous lorazepam in adults with convulsive status epilepticus without established intravenous access (Level A). In children, intravenous lorazepam and intravenous diazepam are established as efficacious at stopping seizures lasting at least 5 minutes (Level A) while rectal diazepam, intramuscular midazolam, intranasal midazolam, and buccal midazolam are probably effective (Level B). No significant difference in effectiveness has been demonstrated between intravenous lorazepam and intravenous diazepam in adults or children with convulsive status epilepticus (Level A). Respiratory and cardiac symptoms are the most commonly encountered treatment-emergent adverse events
Glauser, Tracy; Shinnar, Shlomo; Gloss, David; Alldredge, Brian; Arya, Ravindra; Bainbridge, Jacquelyn; Bare, Mary; Bleck, Thomas; Dodson, W Edwin; Garrity, Lisa; Jagoda, Andy; Lowenstein, Daniel; Pellock, John; Riviello, James; Sloan, Edward; Treiman, David M
The optimal pharmacologic treatment for early convulsive status epilepticus is unclear. To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm. Structured literature review using MEDLINE, Embase, Current Contents, and Cochrane library supplemented with article reference lists. Randomized controlled trials of anticonvulsant treatment for seizures lasting longer than 5 minutes. Individual studies were rated using predefined criteria and these results were used to form recommendations, conclusions, and an evidence-based treatment algorithm. A total o