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Increased volume of cerebral oedema is associated with risk of acute seizure activity and adverse neurological outcomes in encephalitis – regional and volumetric analysis in a multi-centre cohort

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, The Author(s). Background: Seizures can occur unpredictably in patients with acute encephalitis syndrome (AES), and many suffer from poor long-term neurological sequelae. Establishing factors associated with acute seizures risk and poor outcomes could support clinical care. We aimed to conduct regional and volumetric analysis of cerebral oedema on magnetic resonance imaging (MRI) in patients with AES. We assessed the relationship of brain oedema with acute seizure activity and long-term neurological outcome. Methods: In a multi-centre cohort study, adults and children presenting with an AES were recruited in the UK. The clinical and brain MRI data were retrospectively reviewed. The outcomes variables were inpatient acute seizure activity and neurological disability at six-months post-discharge. A poor outcome was defined as a Glasgow outcome score (GOS) of 1–3. We quantified regional brain oedema on MRI through stereological examination of T2-weighted images using established methodology by independent and blinded assessors. Clinical and neuroimaging variables were analysed by multivariate logistic regression to assess for correlation with acute seizure activity and outcome. Results: The study cohort comprised 69 patients (mean age 31.8 years; 53.6% female), of whom 41 (59.4%) had acute seizures as inpatients. A higher Glasgow coma scale (GCS) score on admission was a negative predictor of seizures (OR 0.61 [0.46–0.83], p = 0.001). Even correcting for GCS on admission, the presence of cortical oedema was a significant risk factor for acute seizure activity (OR 5.48 [1.62–18.51], p = 0.006) and greater volume of cerebral oedema in these cortical structures increased the risk of acute seizures (OR 1.90 [1.12–3.21], p = 0.017). At six-month post-discharge, 21 (30.4%) had a poor neurological outcome. Herpes simplex virus encephalitis was associated with higher risk of poor outcomes in univariate analysis (OR 3.92 [1.08–14.20], p = 0.038). When controlling for aetiology, increased volume of cerebral oedema was an independent risk factor for adverse neurological outcome at 6 months (OR 1.73 [1.06–2.83], p = 0.027). Conclusions: Both the presence and degree of cerebral oedema on MRIs of patients with AES may help identify patients at risk of acute seizure activity and subsequent long-term morbidity.

Publication metadata

Author(s): Alam AM, Chen JPK, Wood GK, Facer B, Bhojak M, Das K, Defres S, Marson A, Granerod J, Brown D, Thomas RH, Keller SS, Solomon T, Michael BD

Publication type: Article

Publication status: Published

Journal: BMC Neurology

Year: 2022

Volume: 22

Issue: 1

Online publication date: 07/11/2022

Acceptance date: 17/10/2022

Date deposited: 24/11/2022

ISSN (electronic): 1471-2377

Publisher: BioMed Central Ltd


DOI: 10.1186/s12883-022-02926-5


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Funder referenceFunder name
MR/ V03605X/1