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How much refractory is ‘refractory status epilepticus’? A retrospective study of treatment strategies and clinical outcomes

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Abstract

Background and purpose

This study aimed to evaluate whether differences in clinical outcomes exist according to treatments received and seizure activity resolution in patients with refractory status epilepticus (RSE).

Methods

Consecutive episodes of non-hypoxic status epilepticus (SE) in patients ≥ 14 years old were included. Episodes of RSE were stratified in: (i) SE persistent despite treatment with first‐line therapy with benzodiazepines and one second‐line treatment with antiseizure medications (ASMs), but responsive to successive treatments with ASMs (RSE-rASMs); (ii) SE persistent despite treatment with first‐line therapy with benzodiazepines and successive treatment with one or more second-line ASMs, but responsive to anesthetic drugs [RSE-rGA (general anesthesia)]. Study endpoints were mortality during hospitalization and worsening of modified Rankin Scale (mRS) at discharge.

Results

Status epilepticus was responsive in 298 (54.1%), RSE-rASMs in 152 (27.6%), RSE-rGA in 46 (8.3%), and super-refractory (SRSE) in 55 (10.0%) out of 551 included cases. Death during hospitalization occurred in 98 (17.8%) and worsening of mRS at discharge in 287 (52.1%) cases. Multivariable analyses revealed increased odds of in-hospital mortality with RSE-rGA (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.27–7.35) and SRSE (OR 3.83, 95%. CI 1.73–8.47), and increased odds of worsening of mRS with RSE-rASMs (OR 2.06, 95% CI 1.28–3.31), RSE-rGA (OR 4.44, 95% CI 1.97–10.00), and SRSE (OR 13.81, 95% CI 5.34–35.67).

Conclusions

In RSE, varying degrees of refractoriness may be defined and suit better the continuum spectrum of disease severity and the heterogeneity of SE burden and prognosis.

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Data availability

Anonymized data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The study received funding by the Italian MOH: “Status epilepticus: improving therapeutic and quality of care intervention in the Emilia-Romagna region”. Project code: RF-2016-02361365. Supported by a grant “Dipartimento di eccellenza 2018-2022”, MIUR, Italy, to the Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia.

Author information

Authors and Affiliations

  1. Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Via Conca 71, 60020, Ancona, Italy

    Simona Lattanzi

  2. Neurology Unit, OCB Hospital, AOU Modena, Modena, Italy

    Giada Giovannini, Niccolò Orlandi & Stefano Meletti

  3. Department of Biomedical, Metabolic and Neural Science, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Via Giardini, 1355, Ospedale Civile S. Agostino Estense, 41126, Modena, Italy

    Niccolò Orlandi & Stefano Meletti

  4. Division of Neurology, “Franz Tappeiner” Hospital, Merano, BZ, Italy

    Francesco Brigo

  5. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria

    Eugen Trinka

  6. Center for Cognitive Neuroscience, Salzburg, Austria

    Eugen Trinka

  7. Public Health, Health Services Research and HTA, University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria

    Eugen Trinka

Authors
  1. Simona Lattanzi
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  2. Giada Giovannini
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  3. Niccolò Orlandi
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  4. Francesco Brigo
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  5. Eugen Trinka
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  6. Stefano Meletti
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Contributions

SL planned and designed the study, performed the statistical analyses, interpreted the data, and drafted the manuscript. GG and NO acquired and interpreted the data, revised the manuscript, and contributed to the inaugural draft. FB and ET revised the manuscript, and contributed to the inaugural draft. SM planned and designed the study, interpreted the data, revised the manuscript, and contributed to the inaugural draft. All authors approved the final submitted version.

Corresponding authors

Correspondence to Simona Lattanzi or Stefano Meletti.

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Conflicts of interest

Simona Lattanzi has received speaker’s or consultancy fees from Angelini Pharma, Eisai, GW Pharmaceuticals, and UCB Pharma and has served on advisory boards for Angelini Pharma, Arvelle Therapeutics, BIAL, Eisai, GW Pharmaceuticals, and Rapport Therapeutics outside the submitted work. Eugen Trinka has received consultancy fees from Arvelle Therapeutics, Argenx, Clexio, Celegene, UCB Pharma, Eisai, Epilog, Bial, Medtronic, Everpharma, Biogen, Takeda, Liva-Nova, Newbridge, Sunovion, GW Pharmaceuticals, and Marinus; speaker fees from Arvelle Therapeutics, Bial, Biogen, Böhringer Ingelheim, Eisai, Everpharma, GSK, GW Pharmaceuticals, Hikma, Liva-Nova, Newbridge, Novartis, Sanofi, Sandoz and UCB Pharma; research funding (directly, or to his institution) from GSK, Biogen, Eisai, Novartis, Red Bull, Bayer, and UCB Pharma outside the submitted work. Eugen Trinka receives Grants from Austrian Science Fund (FWF), Österreichische Nationalbank, and the European Union. Eugen Trinka is the CEO of Neuroconsult Ges.m.b.H. Stefano Meletti received research grant support from the Ministry of Health (MOH) and the non-profit organization Foundation “Fondazione Cassa di Risparmio di Modena—FCRM”; has received personal compensation as scientific advisory board member for UCB, Jazz Pharmaceuticals, and EISAI outside the submitted work. The remaining authors have no conflicts of interest.

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Lattanzi, S., Giovannini, G., Orlandi, N. et al. How much refractory is ‘refractory status epilepticus’? A retrospective study of treatment strategies and clinical outcomes. J Neurol 270, 6133–6140 (2023). https://doi.org/10.1007/s00415-023-11929-2

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  • DOI: https://doi.org/10.1007/s00415-023-11929-2

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