Acute seizure risk in patients with encephalitis: development and validation of clinical prediction models from two independent prospective multicentre cohorts

Greta K Wood; Roshan Babar; Mark A Ellul; Rhys Huw Thomas; Harriet Van Den Tooren; Ava Easton; Kukatharmini Tharmaratnam; Girvan Burnside; Ali M Alam; Hannah Castell; Sarah Boardman; Ceryce Collie; Bethany Facer; Cordelia Dunai; Sylviane Defres; Julia Granerod; David W G Brown; Angela Vincent; Anthony Guy Marson; Sarosh R Irani; Tom Solomon; Benedict D Michael

doi:10.1136/bmjno-2022-000323

Acute seizure risk in patients with encephalitis: development and validation of clinical prediction models from two independent prospective multicentre cohorts

BMJ Neurol Open. 2022 Sep 5;4(2):e000323. doi: 10.1136/bmjno-2022-000323. eCollection 2022.

Authors

Greta K Wood^{1

2}, Roshan Babar¹, Mark A Ellul^{1

3}, Rhys Huw Thomas^{4

5}, Harriet Van Den Tooren¹, Ava Easton^{6

7}, Kukatharmini Tharmaratnam⁸, Girvan Burnside⁸, Ali M Alam^{1

2}, Hannah Castell^{1

9}, Sarah Boardman^{1

2}, Ceryce Collie^{1

2}, Bethany Facer^{1

2}, Cordelia Dunai^{1

2}, Sylviane Defres^{1

10}, Julia Granerod¹¹, David W G Brown¹², Angela Vincent¹³, Anthony Guy Marson^{3

14}, Sarosh R Irani¹³, Tom Solomon^{1

2}, Benedict D Michael^{1

2}

Affiliations

¹ Institute of Infection, Veterinary, and Ecological Science, University of Liverpool Department of Clinical Infection Microbiology and Immunology, Liverpool, UK.
² NIHR Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool, Liverpool, UK.
³ Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UK.
⁴ Faculty of Medical Sciences, Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK.
⁵ Neurosciences, Royal Victoria Infirmary, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK.
⁶ Encephalitis Society, Malton, UK.
⁷ University of Liverpool Department of Clinical Infection Microbiology and Immunology, Liverpool, UK.
⁸ Department of Health Data Science, University of Liverpool Faculty of Health and Life Sciences, Liverpool, UK.
⁹ Institute of Infection, Veterinary, and Ecological Science, NIHR Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool, Liverpool, UK.
¹⁰ Tropical and Infectious Diseases Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
¹¹ UK Health Security Agency, London, UK.
¹² Virus Reference Department, UK Health Security Agency, London, UK.
¹³ Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK.
¹⁴ Department of Pharmacology and Therapeutics, University of Liverpool Institute of Systems, Molecular and Integrative Biology, Liverpool, UK.

Abstract

Objective: In patients with encephalitis, the development of acute symptomatic seizures is highly variable, but when present is associated with a worse outcome. We aimed to determine the factors associated with seizures in encephalitis and develop a clinical prediction model.

Methods: We analysed 203 patients from 24 English hospitals (2005-2008) (Cohort 1). Outcome measures were seizures prior to and during admission, inpatient seizures and status epilepticus. A binary logistic regression risk model was converted to a clinical score and independently validated on an additional 233 patients from 31 UK hospitals (2013-2016) (Cohort 2).

Results: In Cohort 1, 121 (60%) patients had a seizure including 103 (51%) with inpatient seizures. Admission Glasgow Coma Scale (GCS) ≤8/15 was predictive of subsequent inpatient seizures (OR (95% CI) 5.55 (2.10 to 14.64), p<0.001), including in those without a history of prior seizures at presentation (OR 6.57 (95% CI 1.37 to 31.5), p=0.025).A clinical model of overall seizure risk identified admission GCS along with aetiology (autoantibody-associated OR 11.99 (95% CI 2.09 to 68.86) and Herpes simplex virus 3.58 (95% CI 1.06 to 12.12)) (area under receiver operating characteristics curve (AUROC) =0.75 (95% CI 0.701 to 0.848), p<0.001). The same model was externally validated in Cohort 2 (AUROC=0.744 (95% CI 0.677 to 0.811), p<0.001). A clinical scoring system for stratifying inpatient seizure risk by decile demonstrated good discrimination using variables available on admission; age, GCS and fever (AUROC=0.716 (95% CI 0.634 to 0.798), p<0.001) and once probable aetiology established (AUROC=0.761 (95% CI 0.6840.839), p<0.001).

Conclusion: Age, GCS, fever and aetiology can effectively stratify acute seizure risk in patients with encephalitis. These findings can support the development of targeted interventions and aid clinical trial design for antiseizure medication prophylaxis.

Keywords: AUTOIMMUNE ENCEPHALITIS; CLINICAL NEUROLOGY; INFECTIOUS DISEASES.

Abstract

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