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Although status epilepticus (SE) does not resemble a domain for neurosurgical indications in single occasions, a microneurosurgical procedure in patients with catastrophic epilepsy and status epilepticus should be considered as an ultimate ratio‐choice in these patients. From a personal series of >600 epilepsy surgery procedures in a period from August 1, 1993 until March 13, 2013, 22 patients...
A significant number of patients with epilepsy fail to respond to currently available antiepileptic drugs. This suggests a need for alternative approaches to reduce the occurrence of seizures in these patients. Recent data have shown that in addition to well‐known neuronal mechanism, seizures may be a consequence of misguided inflammatory response and blood–brain barrier disruption. Both peripheral...
In this article, the three previous London‐Innsbruck Colloquia on Status Epilepticus are reviewed. The background to the colloquia and the range of topics covered in each colloquium are outlined. The areas in which advances in the study of status epilepticus, and also areas in which advances have been disappointing are highlighted.
The homeostatic bioenergetic network regulator adenosine is an endogenous anticonvulsant of the brain that plays critical roles in seizure termination and postictal refractoriness. Adenosine homeostasis in the adult brain is largely under the control of metabolic clearance through adenosine kinase (ADK), expressed predominantly in astrocytes. The role of adenosine in status epilepticus (SE) appears...
Early treatment of prolonged seizures with benzodiazepines given intravenously by paramedics in the prehospital setting had been shown to be associated with improved outcomes, but the comparative efficacy and safety of an intramuscular (IM) route, which is faster and consistently achievable, was previously unknown. RAMPART (the Rapid Anticonvulsant Medication Prior to Arrival Trial) was a double‐blind...
We used two models of status epilepticus (SE) to study trafficking of N‐methyl‐d‐aspartate (NMDA) receptors. SE is associated with increased surface expression of NR1 subunits of NMDA receptors, and with an increase of NMDA synaptic and extrasynaptic currents suggesting an increase in number of functional NMDA receptors on dentate granule cells. The therapeutic implications of these results are discussed.
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 benzodiazepine...
sec‐Butyl‐propylacetamide (SPD) is a one‐carbon homolog of valnoctamide (VCD), a chiral constitutional isomer of valproic acid's (VPA) corresponding amide valpromide. VCD has potential as a therapy in epilepsy including status epilepticus (SE) and neuropathic pain, and is currently being developed for the treatment of bipolar disorder. Both VCD and SPD possess two stereogenic carbons in their chemical...
Status epilepticus (SE) is common in sub‐Saharan Africa, particularly in children. Most cases in children are caused by infections, particularly malaria in endemic areas. The outcome is worse than in the West, probably because of delays in initiating treatment, and lack of skills and facilities for the management of SE. However some of the causes, for example, falciparum malaria, offer challenges...
Neurogenesis in the adult central nervous system has been well documented in several mammals including humans. By now, a plethora of data has been generated with the aim of understanding the molecular and cellular events governing neurogenesis. This growing comprehension will provide the basis for modulation of neurogenesis for therapeutic purposes, in particular in neurodegenerative diseases. Herein,...
There is a remarkable dearth of information about the various therapies used, often widely so, to control refractory or super‐refractory status epilepticus despite its high mortality and morbidity. As pointed out by recent literature reviews, there are no controlled studies, and information is based almost entirely on open, often small and retrospective, case series or case reports. Randomized or...
After seizures have been controlled, long‐term care of status epilepticus may be needed and collectively involves every major organ. First, as a result of rapid escalation of antiepileptic drugs, there are initial concerns with hypotension, acid‐base abnormalities, and cardiac arrhythmias. Second, refractory status epilepticus and the continuous need for intravenous administration of anesthetic drugs...
Focal cortical dysplasia (FCD) is a brain malformation associated with particularly severe drug‐resistant epilepsy that often requires surgery for seizure control. The molecular basis for such enhanced propensity to seizure generation in FCD is not as yet elucidated. To investigate cellular and molecular bases of epileptogenic mechanisms and possible effect of severe epilepsy on the malformed cortex...
Benzodiazepine‐refractory status epilepticus (established status epilepticus, ESE) is a relatively common emergency condition with several widely used treatments. There are no controlled, randomized, blinded clinical trials to compare the efficacy and tolerability of currently available treatments for ESE. The ESE treatment trial is designed to determine the most effective and/or the least effective...
Nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE) are electrographic seizures (ESz) that are not associated with overt clinical seizure activity. NCS are distinct ESz, whereas NCSE has ongoing, continuous electrographic seizure activity. Both are common in critically ill patients admitted to hospital intensive care units (ICUs), and studies have shown that about 20% of ICU patients...
Refractory status epilepticus (SE) has a mortality rate of up to 35%. Current treatment protocols for the treatment of SE begin with benzodiazepines and then proceed to conventional anticonvulsants. If seizures continue, SE is considered refractory (RSE) and treatment with anesthetic agents in undertaken. Twenty‐four h to 48 h after initiation of anesthesia with midazolam, pentobarbital or thiopental,...
The recent discovery of a category of autoimmune encephalitis associated with antibodies against neuronal cell‐surface and synaptic proteins has renewed interest for autoimmune causes of epilepsy. The identification of autoimmune encephalitis has changed paradigms in the diagnosis and management of several novel and treatable syndromes that occur with seizures and status epilepticus previously attributed...
The evolution of the treatment of convulsive status epilepticus since the mid‐ nineteenth century is outlined. Therapy has been advanced not only by the use of new drugs, but also by advances in the approach to therapy. The major pharmacologic developments were the introductions of bromide, anesthetics, barbiturate, phenytoin, paraldehyde, chlormethiazole, and the benzodiazepines. Throughout this...
Gene therapy in human disease has expanded rapidly in recent years with the development of safer and more effective viral vectors, and presents a novel approach to the treatment of epilepsy. Studies in animals models have demonstrated that overexpression of inhibitory peptides can modify seizure threshold, prevent the development of epilepsy, and modify established epilepsy. More recently there has...
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