title: Characterising seizures in anti-NMDA-receptor encephalitis with dynamic causal modelling.
abstract: We characterised the pathophysiology of seizure onset in terms of slow fluctuations in synaptic efficacy using EEG in patients with anti-N-methyl-d-aspartate receptor (NMDA-R) encephalitis. EEG recordings were obtained from two female patients with anti-NMDA-R encephalitis with recurrent partial seizures (ages 19 and 31). Focal electrographic seizure activity was localised using an empirical Bayes beamformer. The spectral density of reconstructed source activity was then characterised with dynamic causal modelling (DCM). Eight models were compared for each patient, to evaluate the relative contribution of changes in intrinsic (excitatory and inhibitory) connectivity and endogenous afferent input. Bayesian model comparison established a role for changes in both excitatory and inhibitory connectivity during seizure activity (in addition to changes in the exogenous input). Seizures in both patients were associated with a sequence of changes in inhibitory and excitatory connectivity; a transient increase in inhibitory connectivity followed by a transient increase in excitatory connectivity and a final peak of excitatory-inhibitory balance at seizure offset. These systematic fluctuations in excitatory and inhibitory gain may be characteristic of (anti NMDA-R encephalitis) seizures. We present these results as a case study and replication to motivate analyses of larger patient cohorts, to see whether our findings generalise and further characterise the mechanisms of seizure activity in anti-NMDA-R encephalitis.
authors.affiliation: Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, UK; Clinical Neurophysiology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: gerald.cooray@ki.se.
authors.forename: Gerald K
authors.initials: GK
authors.lastname: Cooray
authors.affiliation: Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, UK.
authors.forename: Biswa
authors.initials: B
authors.lastname: Sengupta
authors.affiliation: Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, UK.
authors.forename: Pamela
authors.initials: P
authors.lastname: Douglas
authors.affiliation: Clinical Neurophysiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Marita
authors.initials: M
authors.lastname: Englund
authors.affiliation: Neuropediatric Unit, Department of Women's and Children's Health, Karolinska Institutet, Sweden.
authors.forename: Ronny
authors.initials: R
authors.lastname: Wickstrom
authors.affiliation: Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, UK.
authors.forename: Karl
authors.initials: K
authors.lastname: Friston
mesh_terms: D000328:Adult; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000150:complications* / Q000503:physiopathology*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008959:Models, Neurological; D012640:Seizures / Q000209:etiology* / Q000503:physiopathology*; D012815:Signal Processing, Computer-Assisted; D055815:Young Adult
keywords: Anti-NMDA-R encephalitis; Dynamical causal modelling (DCM); EEG; Seizures