Toggle Main Menu Toggle Search

Open Access padlockePrints

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

Lookup NU author(s): Dr Rhys ThomasORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022 Author(s) (or their employer(s)). 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.

Publication metadata

Author(s): Wood GK, Babar R, Ellul MA, Thomas RH, Van Den Tooren H, Easton A, Tharmaratnam K, Burnside G, Alam AM, Castell H, Boardman S, Collie C, Facer B, Dunai C, Defres S, Granerod J, Brown DWG, Vincent A, Marson AG, Irani SR, Solomon T, Michael BD

Publication type: Article

Publication status: Published

Journal: BMJ Neurology Open

Year: 2022

Volume: 4

Issue: 2

Online publication date: 05/09/2022

Acceptance date: 23/08/2022

Date deposited: 04/10/2022

ISSN (electronic): 2632-6140

Publisher: BMJ Publishing Group


DOI: 10.1136/bmjno-2022-000323


Altmetrics provided by Altmetric


Funder referenceFunder name
Department of Health Policy Research Programme (Enhanced Diagnostic and Management Strategies to Improve the Identification and Outcome of Individuals with Encephalitis)