Laurent M Willems1,2,3, Sebastian Bauer4,5,6, Kolja Jahnke5, Martin Voss5,7,8, Felix Rosenow4,5,6, Adam Strzelczyk4,5,6,9. 1. Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, Goethe-University Frankfurt, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany. laurent.willems@kgu.de. 2. Department of Neurology, Goethe University Frankfurt, Frankfurt am Main, Germany. laurent.willems@kgu.de. 3. LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe University Frankfurt, Frankfurt am Main, Germany. laurent.willems@kgu.de. 4. Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, Goethe-University Frankfurt, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany. 5. Department of Neurology, Goethe University Frankfurt, Frankfurt am Main, Germany. 6. LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe University Frankfurt, Frankfurt am Main, Germany. 7. Dr. Senckenberg Institute of Neuro-Oncology, Goethe University Frankfurt, University Hospital Frankfurt, Frankfurt am Main, Germany. 8. Frankfurt Cancer Institute (FCI), Goethe University Frankfurt, Frankfurt am Main, Germany. 9. Department of Neurology, Epilepsy Center Hessen, Philipps University Marburg, Marburg (Lahn), Germany.
Abstract
BACKGROUND: Refractory status epilepticus (RSE) represents a serious medical condition requiring early and targeted therapy. Given the increasing number of elderly or multimorbid patients with a limitation of life-sustaining therapy (LOT) or within a palliative care setting (PCS), guidelines-oriented therapy escalation options for RSE have to be omitted frequently. OBJECTIVES: This systematic review sought to summarize the evidence for fourth-line antiseizure drugs (ASDs) and other minimally or non-invasive therapeutic options beyond guideline recommendations in patients with RSE to elaborate on possible treatment options for patients undergoing LOT or in a PCS. METHODS: A systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on fourth-line ASDs or other minimally or non-invasive therapeutic options was performed in February and June 2020 using the MEDLINE, EMBASE and Cochrane databases. The search terminology was constructed using the name of the specific ASD or therapy option and the term 'status epilepticus' with the use of Boolean operators, e.g. "(brivaracetam) AND (status epilepticus)". The respective Medical Subject Headings (MeSH) and Emtree terms were used, if available. RESULTS: There is currently no level 1, grade A evidence for the use of ASDs in RSE. The best evidence was found for the use of lacosamide and topiramate (level 3, grade C), followed by brivaracetam, perampanel (each level 4, grade D) and stiripentol, oxcarbazepine and zonisamide (each level 5, grade D). Regarding non-medicinal options, there is little evidence for the use of the ketogenic diet (level 4, grade D) and magnesium sulfate (level 5, grade D) in RSE. The broad use of immunomodulatory or immunosuppressive treatment options in the absence of a presumed autoimmune etiology cannot be recommended; however, if an autoimmune etiology is assumed, steroid pulse, intravenous immunoglobulins and plasma exchange/plasmapheresis should be considered (level 4, grade D). Even if several studies suggested that the use of neurosteroids (level 5, grade D) is beneficial in RSE, the current data situation indicates that there is formal evidence against it. CONCLUSIONS: RSE in patients undergoing LOT or in a PCS represents a challenge for modern clinicians and epileptologists. The evidence for the use of ASDs in RSE beyond that in current guidelines is low, but several effective and well-tolerated options are available that should be considered in this patient population. More so than in any other population, advance care planning, advance directives, and medical ethical aspects have to be considered carefully before and during therapy.
BACKGROUND:Refractory status epilepticus (RSE) represents a serious medical condition requiring early and targeted therapy. Given the increasing number of elderly or multimorbidpatients with a limitation of life-sustaining therapy (LOT) or within a palliative care setting (PCS), guidelines-oriented therapy escalation options for RSE have to be omitted frequently. OBJECTIVES: This systematic review sought to summarize the evidence for fourth-line antiseizure drugs (ASDs) and other minimally or non-invasive therapeutic options beyond guideline recommendations in patients with RSE to elaborate on possible treatment options for patients undergoing LOT or in a PCS. METHODS: A systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on fourth-line ASDs or other minimally or non-invasive therapeutic options was performed in February and June 2020 using the MEDLINE, EMBASE and Cochrane databases. The search terminology was constructed using the name of the specific ASD or therapy option and the term 'status epilepticus' with the use of Boolean operators, e.g. "(brivaracetam) AND (status epilepticus)". The respective Medical Subject Headings (MeSH) and Emtree terms were used, if available. RESULTS: There is currently no level 1, grade A evidence for the use of ASDs in RSE. The best evidence was found for the use of lacosamide and topiramate (level 3, grade C), followed by brivaracetam, perampanel (each level 4, grade D) and stiripentol, oxcarbazepine and zonisamide (each level 5, grade D). Regarding non-medicinal options, there is little evidence for the use of the ketogenic diet (level 4, grade D) and magnesium sulfate (level 5, grade D) in RSE. The broad use of immunomodulatory or immunosuppressive treatment options in the absence of a presumed autoimmune etiology cannot be recommended; however, if an autoimmune etiology is assumed, steroid pulse, intravenous immunoglobulins and plasma exchange/plasmapheresis should be considered (level 4, grade D). Even if several studies suggested that the use of neurosteroids (level 5, grade D) is beneficial in RSE, the current data situation indicates that there is formal evidence against it. CONCLUSIONS: RSE in patients undergoing LOT or in a PCS represents a challenge for modern clinicians and epileptologists. The evidence for the use of ASDs in RSE beyond that in current guidelines is low, but several effective and well-tolerated options are available that should be considered in this patient population. More so than in any other population, advance care planning, advance directives, and medical ethical aspects have to be considered carefully before and during therapy.
Authors: Eugen Trinka; Hannah Cock; Dale Hesdorffer; Andrea O Rossetti; Ingrid E Scheffer; Shlomo Shinnar; Simon Shorvon; Daniel H Lowenstein Journal: Epilepsia Date: 2015-09-04 Impact factor: 5.864