Case Reports in Neurological Medicine

Case Reports in Neurological Medicine / 2019 / Article

Case Report | Open Access

Volume 2019 |Article ID 8537815 |

Abdallah Rahbani, Grace Adwane, Najo Jomaa, "Oral Perampanel for the Treatment of Super-Refractory Status Epilepticus", Case Reports in Neurological Medicine, vol. 2019, Article ID 8537815, 3 pages, 2019.

Oral Perampanel for the Treatment of Super-Refractory Status Epilepticus

Academic Editor: Dennis J. Rivet
Received14 Oct 2018
Accepted27 Mar 2019
Published09 Apr 2019


A 72-year-old man presented with a super-refractory partial status epilepticus following evacuation of a right subdural hematoma. He failed to respond to treatment with high doses of intravenous valproic acid, Levetiracetam, Lacosamide, Thiopental, and Midazolam. He was given 4 mg of Perampanel orally via nasogastric tube and the dose was rapidly increased to 8 mg after 12 hours with cessation of clinical and electrical seizures. Other antiepileptic drugs were tapered progressively with an excellent clinical outcome.

1. Background

This is a case of super-refractory status epilepticus which responded to high doses of Perampanel, therefore highlighting the role of AMPA receptor antagonists in prolonged status epilepticus and the beneficial role of Perampanel in these special cases.

2. Clinical Presentation

A 72-year-old hypertensive and diabetic patient presented to the emergency department with left arm numbness and weakness ten days following evacuation of right subdural hematoma. Computed tomography scan of the brain showed partial regression of the right subdural hematoma and its mass effect but with a new hyperdense component suggesting acute bleeding. This was completed by a magnetic resonance imaging of the brain that confirmed the presence of an associated cortical edema. The patient was admitted to the intensive care unit for monitoring and was started on intravenous dexamethasone and oral Levetiracetam. Three days following admission the patient started to have clonic jerks involving the left face and the left upper limb in addition to rapid deterioration of his level of consciousness. He was given loading dose of intravenous valproic acid without clinical improvement. He was rapidly intubated and started on high doses of intravenous Midazolam with persistence of clinical seizures which necessitated the addition of intravenous Thiopental, and the patient was put on EEG monitoring. The dose of Levetiracetam was rapidly increased to 3000 mg and the patient was kept on intravenous maintenance dose of valproic acid. Even on optimal doses of Thiopental that induced burst suppression pattern on the electroencephalogram, the patient was still having recurrent and brief partial seizures that were clinically and electrically evident. Intravenous Lacosamide was added (200 mg twice per day) without any major effect. 24 hours later, in presence of recurrent seizures even on optimal doses of Thiopental, the patient received 4 mg of Perampanel via a nasogastric tube and another 4 mg was given 12 hours later, which induced total resolution of clinical and electrical seizures. The patient was maintained on 8 mg of Perampanel daily. Sedation was progressively decreased and the patient regained progressively a good level of consciousness and was extubated 72 hours later. Valproic acid, Lacosamide, and Levetiracetam doses were progressively decreased and stopped (see Table 1 for details). The patient was discharged home one week later in a relatively very good clinical condition.

Time from seizures beginning.Valproic acidMidazolamThiopentalLevetiracetamLacosamidePerampanel

5 Minutes40 mg/kg loading dose followed by 500 mg intravenously every 6 hours

20 Minutes0.2 mg/kg loading dose titrated to 1.5 mg/kg/hour intravenously1.5 g every 12 hours per nasogastric tube

60 Minutes3 g/24 hours intravenously till burst suppression on EEG.

3 Hours200 mg intravenously every 12 hours

24 Hours4 mg per nasogastric tube

36 Hours4 mg per nasogastric tube

48 HoursTapering till stoppedTapering till stopped8 mg per day

72 Hours and beyondTapering till stoppedTapering till stoppedTapering till stoppedMaintenance dose of 8 mg per day

3. Discussion

Status epilepticus results from an imbalance between persistent cellular excitation mediated by excitatory neurotransmitters “glutamate” and failure of inhibitory synaptic transmission mediated by gamma-amino butyric acid “GABA” [13].

As the status epilepticus continues, it becomes more resistant to treatment secondary to the internalization of the postsynaptic GABA receptors to the cytoplasm, externalization of the NMDA and AMPA receptors to the surface, and change in chloride homeostasis in addition to an excess of the extracellular glutamate leading to perpetuation of the status via the AMPA receptors [4, 5].

This explains the resistance to those antiepileptic drugs having a GABAergic effect and a possible better response to those drugs acting on the neuroexcitatory receptors (NMDA and AMPA receptors). The effect of Perampanel, a noncompetitive AMPA receptor antagonist, as an adjunctive treatment in refractory status epilepticus has not been largely studied, with the exception of few published data demonstrating a variable range of efficacy [69].

Our case is another example of this molecule’s beneficial effect in super-refractory status epilepticus after failure of five appropriately chosen antiepileptic drugs. This can be encouraging for its use in special cases where response to classic drugs is lacking.

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.


  1. V. Bruno, U. Scapagnini, and P. L. Canonico, “Excitatory amino acids and neurotoxicity,” Functional Neurology, vol. 8, no. 4, pp. 279–292, 1993. View at: Google Scholar
  2. S. E. Hocker, J. W. Britton, J. N. Mandrekar, E. F. Wijdicks, and A. A. Rabinstein, “Predictors of outcome in refractory status epilepticus,” JAMA Neurology, vol. 70, no. 1, pp. 72–77, 2013. View at: Publisher Site | Google Scholar
  3. R. Sutter, S. Marsch, P. Fuhr, and S. Rüegg, “Mortality and recovery from refractory status epilepticus in the intensive care unit: a 7-year observational study,” Epilepsia, vol. 54, no. 3, pp. 502–511, 2013. View at: Publisher Site | Google Scholar
  4. J. W. Y. Chen and C. G. Wasterlain, “Status epilepticus: pathophysiology and management in adults,” The Lancet Neurology, vol. 5, no. 3, pp. 246–256, 2006. View at: Publisher Site | Google Scholar
  5. D. E. Naylor, H. Liu, and C. G. Wasterlain, “Trafficking of GABA(A) receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus,” The Journal of Neuroscience, vol. 25, no. 34, pp. 7724–7733, 2005. View at: Publisher Site | Google Scholar
  6. F. Brigo, S. Lattanzi, A. Rohracher et al., “Perampanel in the treatment of status epilepticus: a systematic review of the literature,” Epilepsy and Behavior, vol. 86, pp. 179–186, 2018. View at: Publisher Site | Google Scholar
  7. B. Fritsch, J. J. Stott, J. Joelle Donofrio, and M. A. Rogawski, “Treatment of early and late kainic acid-induced status epilepticus with the noncompetitive AMPA receptor antagonist GYKI 52446,” Epilepsia, vol. 51, no. 1, pp. 108–117, 2010. View at: Publisher Site | Google Scholar
  8. H.-J. Feng, G. C. Mathews, C. Kao, and R. L. Macdonald, “Alterations of GABA Areceptor function and allosteric modulation during development of status epilepticus,” Journal of Neurophysiology, vol. 99, no. 3, pp. 1285–1293, 2008. View at: Publisher Site | Google Scholar
  9. A. Strzelczyk, S. Knake, R. Kälviäinen et al., “Perampanel for treatment of status epilepticus in Austria, Finland, Germany, and Spain,” Acta Neurologica Scandinavica, vol. 139, no. 4, pp. 369–376, 2019. View at: Publisher Site | Google Scholar

Copyright © 2019 Abdallah Rahbani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

More related articles

 PDF Download Citation Citation
 Download other formatsMore
 Order printed copiesOrder

Related articles

Article of the Year Award: Outstanding research contributions of 2020, as selected by our Chief Editors. Read the winning articles.