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Perampanel Treatment for Refractory Status Epilepticus in a Neurological Intensive Care Unit

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An Invited Editorial Commentary to this article was published on 30 May 2019

Abstract

Background/Objective

Perampanel is a novel anti-epileptic drug (AED) which acts as a non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist to reduce glutamate-mediated postsynaptic excitation. Previous animal studies and a few case reports/series have suggested that it may be effective to treat refractory status epilepticus (RSE).

Methods

We retrospectively reviewed 67 consecutive patients with RSE, of whom 22 received perampanel. The clinical features, epidemiology-based mortality score in status epilepticus, status epilepticus severity score, seizure control, functional outcome, RSE etiology, and electroencephalogram findings were collected. Responder to perampanel was defined as seizure resolution within 4 days of therapy with perampanel being the last AED used plus no recurrence during hospitalization.

Results

Eight of the 22 (36.4%) RSE patients fulfilled the definition of responder to perampanel. An additional 1 patient responded to perampanel after 4 days of treatment. In total, perampanel was the last AED in 9 (40.1%) patients. Among the 8 responders to perampanel, 5 had convulsive SE, 1 had non-convulsive SE, and 2 had focal motor SE. The responders accounted for both of the patients with focal motor SE (100%), 5 (33.3%) of the 15 patients with convulsive SE, and 1 (20%) of the 5 patients with non-convulsive SE. The ictal and inter-ictal activities also decreased after perampanel therapy, and three patients (13.6%) had preferable outcomes at last follow-up.

Conclusions

Perampanel may be an effective add-on treatment for RSE even in patients who failed multiple AEDs. Our study suggests that perampanel may be more effective for focal motor SE and convulsive SE than non-convulsive SE. As most previous studies have focused on non-convulsive SE, further studies are warranted to clarify the effectiveness of perampanel for different subtypes of SE.

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References

  1. Tsai MH, Chuang YC, Chang HW, et al. Factors predictive of outcome in patients with de novo status epilepticus. QJM. 2009;102(1):57–62.

    Article  Google Scholar 

  2. Trinka E, Cock H, Hesdorffer D, et al. A definition and classification of status epilepticus–report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015;56(10):1515–23.

    Article  Google Scholar 

  3. Vilella L, Gonzalez Cuevas M, Quintana Luque M, et al. Prognosis of status epilepticus in elderly patients. Acta Neurol Scand. 2018;137(3):321–8.

    Article  CAS  Google Scholar 

  4. Hocker SE, Britton JW, Mandrekar JN, Wijdicks EF, Rabinstein AA. Predictors of outcome in refractory status epilepticus. JAMA Neurol. 2013;70(1):72–7.

    Article  Google Scholar 

  5. Kantanen AM, Reinikainen M, Parviainen I, et al. Incidence and mortality of super-refractory status epilepticus in adults. Epilepsy Behav. 2015;49:131–4.

    Article  Google Scholar 

  6. Strzelczyk A, Ansorge S, Hapfelmeier J, et al. Costs, length of stay, and mortality of super-refractory status epilepticus: a population-based study from Germany. Epilepsia. 2017;58(9):1533–41.

    Article  Google Scholar 

  7. Hamil NE, Cock HR, Walker MC. Acute down-regulation of adenosine A(1) receptor activity in status epilepticus. Epilepsia. 2012;53(1):177–88.

    Article  CAS  Google Scholar 

  8. Leo A, Giovannini G, Russo E, Meletti S. The role of AMPA receptors and their antagonists in status epilepticus. Epilepsia. 2018;59(6):1098–108.

    Article  Google Scholar 

  9. Vargas-Sanchez K, Mogilevskaya M, Rodriguez-Perez J, et al. Astroglial role in the pathophysiology of status epilepticus: an overview. Oncotarget. 2018;9(42):26954–76.

    Article  Google Scholar 

  10. Walker MC. Pathophysiology of status epilepticus. Neurosci Lett. 2018;667:84–91.

    Article  CAS  Google Scholar 

  11. Rajasekaran K, Todorovic M, Kapur J. Calcium-permeable AMPA receptors are expressed in a rodent model of status epilepticus. Ann Neurol. 2012;72(1):91–102.

    Article  CAS  Google Scholar 

  12. Rosche J, Kampf C, Benecke R. Possible effect of perampanel on focal status epilepticus after generalized tonic-clonic status epilepticus. Acta Neurol Belg. 2014;114(3):243–4.

    Article  Google Scholar 

  13. Redecker J, Wittstock M, Benecke R, Rosche J. Efficacy of perampanel in refractory nonconvulsive status epilepticus and simple partial status epilepticus. Epilepsy Behav. 2015;45:176–9.

    Article  Google Scholar 

  14. Rohracher A, Hofler J, Kalss G, et al. Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit. Epilepsy Behav. 2015;49:354–8.

    Article  CAS  Google Scholar 

  15. Rohracher A, Kalss G, Neuray C, et al. Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit: a single-center audit of 30 patients. Epilepsia. 2018​;59(52):​234–42.

    Article  CAS  Google Scholar 

  16. Santamarina E, Sueiras M, Lidon RM, et al. Use of perampanel in one case of super-refractory hypoxic myoclonic status: case report. Epilepsy Behav Case Rep. 2015;4:56–9.

    Article  Google Scholar 

  17. Leitinger M, Beniczky S, Rohracher A, et al. Salzburg consensus criteria for non-convulsive status epilepticus–approach to clinical application. Epilepsy Behav. 2015;49:158–63.

    Article  CAS  Google Scholar 

  18. Ferlisi M, Shorvon S. The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy. Brain. 2012;135(Pt 8):2314–28.

    PubMed  Google Scholar 

  19. Hirsch LJ, Gaspard N, van Baalen A, et al. Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions. Epilepsia. 2018;59(4):739–44.

    Article  Google Scholar 

  20. Rossetti AO, Logroscino G, Milligan TA, et al. Status Epilepticus Severity Score (STESS): a tool to orient early treatment strategy. J Neurol. 2008;255(10):1561–6.

    Article  Google Scholar 

  21. Leitinger M, Holler Y, Kalss G, et al. Epidemiology-based mortality score in status epilepticus (EMSE). Neurocrit Care. 2015;22(2):273–82.

    Article  CAS  Google Scholar 

  22. Wilson JT, Pettigrew LE, Teasdale GM. Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma. 1998;15(8):573–85.

    Article  CAS  Google Scholar 

  23. Brigo F, Lattanzi S, Rohracher A, et al. Perampanel in the treatment of status epilepticus: a systematic review of the literature. Epilepsy Behav. 2018;86:179–86.

    Article  Google Scholar 

  24. Betjemann JP, Lowenstein DH. Status epilepticus in adults. Lancet Neurol. 2015;14(6):615–24.

    Article  Google Scholar 

  25. Malkin SL, Amakhin DV, Veniaminova EA, et al. Changes of AMPA receptor properties in the neocortex and hippocampus following pilocarpine-induced status epilepticus in rats. Neuroscience. 2016;327:146–55.

    Article  CAS  Google Scholar 

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Funding

The study was supported by grants from Chang Gung Medical Foundation (CMRPG8F0701, CMRPG8G0252) and the Ministry of Science and Technology, Taiwan (MOST107-2314-B-182A-057-MY3), to MHT.

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Authors and Affiliations

  1. Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, 123, Dapi Road, Niaosung District, Kaohsiung, 83301, Taiwan

    Chen-Jui Ho, Chih-Hsiang Lin, Yan-Ting Lu, Che-Wei Hsu, Wan-Chen Tsai & Meng-Han Tsai

  2. Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

    Fu-Yuan Shih

  3. College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Meng-Han Tsai

Authors
  1. Chen-Jui Ho
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  2. Chih-Hsiang Lin
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  3. Yan-Ting Lu
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  4. Fu-Yuan Shih
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  5. Che-Wei Hsu
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  6. Wan-Chen Tsai
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  7. Meng-Han Tsai
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Contributions

CJH, CHL, YTL, FYS, CWH, WCT, and MHT contributed to the acquisition and interpretation of the data and revising the manuscript for intellectual content. CJH and MHT contributed to the design and conceptualization of the study; analysis and interpretation of the data; drafting, revising, and final approval of the manuscript for intellectual content. This manuscript has not been published elsewhere and is not under consideration by another journal.

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Correspondence to Meng-Han Tsai.

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The authors confirm that they have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. This study was approved by the local human research ethics committees (Chang Gung Medical Foundation Institutional Reviewer Board 103-3665B and 201800677B0).

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Ho, CJ., Lin, CH., Lu, YT. et al. Perampanel Treatment for Refractory Status Epilepticus in a Neurological Intensive Care Unit. Neurocrit Care 31, 24–29 (2019). https://doi.org/10.1007/s12028-019-00704-9

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  • DOI: https://doi.org/10.1007/s12028-019-00704-9

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