Recent advances in status epilepticus

Trinka, Eugen; Brigo, Francesco; Shorvon, Simon

doi:10.1097/wco.0000000000000307

Cited by 54 publications

(48 citation statements)

References 106 publications

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“…The fast elimination of seizures, therefore, is an urgent medical need to avoid SE evolution into refractory and superrefractory SE, and for preventing a worse prognosis. 1,6 The rapid termination of benzodiazepine-resistant SE in mice by CPD-4645 was associated with significant improvements in pathologic outcomes, such as reduction of hippocampal and amygdalar cell loss and a rescue of recognition memory deficit. Moreover, the drug was administered 60 min after SE onset, an intervention time compatible with the proposed treatment algorithm for novel drugs for human refractory SE.…”

Section: Discussionmentioning

confidence: 99%

“…1 Approximately 50% of these cases present with no prior diagnosis of epilepsy. 1 About 20% of patients die as a result of SE.…”

Section: Introductionmentioning

confidence: 99%

“…1 Approximately 50% of these cases present with no prior diagnosis of epilepsy. 1 About 20% of patients die as a result of SE. 1 Current standard of care includes treatment with first-or second-line agents (benzodiazepines and standard antiepileptic drugs [AEDs]), followed by additional benzodiazepines and other agents such as barbiturates and propofol to eliminate unremitting seizures as quickly as possible.…”

Section: Introductionmentioning

confidence: 99%

“…1 About 20% of patients die as a result of SE. 1 Current standard of care includes treatment with first-or second-line agents (benzodiazepines and standard antiepileptic drugs [AEDs]), followed by additional benzodiazepines and other agents such as barbiturates and propofol to eliminate unremitting seizures as quickly as possible. 1,2 About one-third of patients still continue seizing despite the treatment, thus evolving to refractory SE, and half of these subsequently develop superrefractory SE, resistant to anesthetic treatment.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 About one-third of patients still continue seizing despite the treatment, thus evolving to refractory SE, and half of these subsequently develop superrefractory SE, resistant to anesthetic treatment. 1 Furthermore, refractory SE is linked to a worse prognosis, both in terms of mortality and morbidity. Decline in intellectual function and cognitive deficits have been reported, particularly in new-onset refractory SE in both children and adults.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of monoacylglycerol lipase terminates diazepam‐resistant status epilepticus in mice and its effects are potentiated by a ketogenic diet

et al. 2017

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SummaryObjective: Status epilepticus (SE) is a life-threatening and commonly drug-refractory condition. Novel therapies are needed to rapidly terminate seizures to prevent mortality and morbidity. Monoacylglycerol lipase (MAGL) is the key enzyme responsible for the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) and a major contributor to the brain pool of arachidonic acid (AA). Inhibiting of monoacylglycerol lipase modulates synaptic activity and neuroinflammation, 2 mediators of excessive neuronal activation underlying seizures. We studied the effect of a potent and selective irreversible MAGL inhibitor, CPD-4645, on SE that was refractory to diazepam, its neuropathologic sequelae, and the mechanism underlying the drug's effects. Methods: Diazepam-resistant SE was induced in adult mice fed with standard or ketogenic diet or in cannabinoid receptor type 1 (CB1) receptor knock-out mice.CPD-4645 (10 mg/kg, subcutaneously) or vehicle was dosed 1 and 7 h after status epilepticus onset in video-electroencephalography (EEG) recorded mice. At the end of SE, mice were examined in the novel object recognition test followed by neuronal cellloss analysis. Results: CPD-4645 maximal plasma and brain concentrations were attained 0.5 h postinjection (half-life = 3.7 h) and elevated brain 2-AG levels by approximately 4-fold. CPD-4645 administered to standard diet-fed mice progressively reduced spike frequency during 3 h postinjection, thereby shortening SE duration by 47%. The drug immediately abrogated SE in ketogenic diet-fed mice. CPD-4645 rescued neuronal cell loss and cognitive deficit and reduced interleukin (IL)-1b and cyclooxygenase 2 (COX-2) brain expression resulting from SE. The CPD-4645 effect on SE was similar in mice lacking CB1 receptors.Gaetano Terrone, Alberto Pauletti, and Alessia Salamone share first authorship. Gaetano Terrone is on leave

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Section: Discussionmentioning

confidence: 99%

“…1 Approximately 50% of these cases present with no prior diagnosis of epilepsy. 1 About 20% of patients die as a result of SE.…”

Section: Introductionmentioning

confidence: 99%