Characterising seizures in anti-NMDA-receptor encephalitis with dynamic causal modelling

Gerald K Cooray,Biswa Sengupta,Pamela Douglas,Marita Englund,Ronny Wickstrom,Karl Friston

doi:10.1016/j.neuroimage.2015.05.064

Gerald K Cooray, Biswa Sengupta + Show 4 more

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https://doi.org/10.1016/j.neuroimage.2015.05.064

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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.

Highlights

Anti-N-methyl-D-aspartate receptor (NMDA-R) antibody encephalitis was discovered in 2007 in several females with ovarian teratoma presenting with psychiatric and dys-autonomous symptoms
The seizure activity of the first patient comprised low amplitude 20 Hz activity, which reduced in frequency to approximately 10 Hz but increased in amplitude
Seizure activity was most prominent over the temporal region on the left side, it showed a rapid and partial spread

Summary

Introduction

Anti-N-methyl-D-aspartate receptor (NMDA-R) antibody encephalitis was discovered in 2007 in several females with ovarian teratoma presenting with psychiatric and dys-autonomous symptoms. The disease has been described in the paediatric population. It is an autoimmune disease with auto-antibodies targeting the NMDA-R (Dalmau et al, 2011). A multicentre study in the UK identified anti-NMDA-R encephalitis in 4% of patients with encephalitis (Granerod et al, 2010), which usually develops through specific phases (Iizuka et al, 2008). There is often a rapid disintegration of language This disease often progresses with neurological symptoms that can include reduced consciousness, oro-lingual-facial dyskinesia, seizures and dysautonomia. At this stage, the patient often requires treatment in an intensive care unit. The frequency and intensity of seizures usually decrease as the disease evolves; changes

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