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Case Reports
. 2014 Dec;76(6):911-5.
doi: 10.1002/ana.24295. Epub 2014 Nov 11.

Pediatric super-refractory status epilepticus treated with allopregnanolone

Eileen Broomall  1 , JoAnne E Natale, Michele Grimason, Joshua Goldstein, Craig M Smith, Celia Chang, Stephen Kanes, Michael A Rogawski, Mark S Wainwright
Affiliations
Case Reports

Pediatric super-refractory status epilepticus treated with allopregnanolone

Eileen Broomall et al. Ann Neurol. 2014 Dec.

Abstract

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.

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Conflict of interest statement

Potential Conflicts of Interest

J.E.N. coinvestigator, Department of Defense–sponsored clinical trial of allopregnanolone in traumatic brain injury; unpaid consultancy, Sage Therapeutics. S.K.: stock option, Sage Therapeutics; employee of Sage Therapeutics, which is conducting an ongoing clinical trial of allopregnanolone for the treatment of SRSE in adults. M.A.R.: advisory board, equity, Sage Therapeutics; principal investigator, Department of Defense–sponsored clinical trial of allopregnanolone in traumatic brain injury. M.S.W.: unpaid consultancy, Sage Therapeutics. The allopregnanolone intravenous formulation was manufactured by the University of California, Davis and was provided free of charge to the treating physicians. The material was not provided by Sage Therapeutics and was not part of a Sage-sponsored clinical trial. Sage Therapeutics is currently developing the formulation of allopregnanolone used in this report for treatment of adults with SRSE and is the sponsor of a clinical trial of this drug in adults with SRSE. None of the authors is a patent holder for relevant inventions.<zbmrule>

Figures

Fig. 1
Fig. 1
(A) Antiseizure and immunomodulatory medications used for Patient 1 by day of hospitalization. Day 0 = admission date. (B) Summary of allopregnanolone infusion protocol used for Patients 1 and 2 with hemodynamic and laboratory monitoring. ALLO = allopregnanolone; CBC = complete blood count; CK = creatine kinase; CLB = clobazam; CPM = cyclophosphamide; DEX = dexamethasone; EEG = electroencephalogram; EKG = electrocardiogram; FBM = felbamate; HYP = mild hypothermia; IVIG = intravenous immunoglobulin; KGD = ketogenic diet; KTM = ketamine; LCS = lacosamide; LFT = liver function testing; LRZ =lorazepam ; LVT = levetiracetam; MDZ = midazolam; MG = magnesium; MPR = methylprednisolone; PB = phenobarbital; PHT = phenytoin; PLEX = plasmapheresis; PRO = propofol; PTB = pentobarbital; RTX = rituximab; TPM = topiramate; VPA = valproate.
Fig. 2
Fig. 2
Allopreganolone plasma concentrations in both patients during allopregnanolone infusion. AQ1: AU: In second paragraph of Acknowledgment, please add “Dr” where appropriate. AQ2: AU: “LFT = liver function testing” and “MPR = methylprednisolone” okay in Fig 1 legend?
See this image and copyright information in PMC

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