Paediatric autoimmune encephalitis (e.g., acute disseminated encephalomyelitis, N-methyl-D-aspartate receptor antibody encephalitis) is an inflammatory brain disease that causes cognitive deficits, psychiatric symptoms, seizures, MRI, and EEG abnormalities. Patients can continue to experience residual cognitive difficulties months to years after the acute illness. Magnetoencephalography (MEG) can examine neural changes in the absence of frank structural abnormalities and may help identify factors predicting children at risk of long-term cognitive deficits. We predicted that theta and delta brain functional connectivity networks would be associated with processing speed and working memory in children with autoimmune encephalitis. Participants were children diagnosed with autoimmune encephalitis at least 18 months before testing and typically developing children. All completed MEG recording (Elekta Neuromag Triux) at rest, eyes open with a fixation cross during six minutes; T1 MRI scans; and cognitive evaluation using the primary subtests of the Weschler Intelligence Scale for Children, fifth edition. Brain connectivity, specifically in delta and theta brain activity, was estimated with amplitude envelope correlation, and network efficiency was measured using graph measures (global efficiency, local efficiency, modularity). The measures were compared across the two groups with permutation correction for multiple thresholds. Finally, statistical associations with processing speed and working memory scores were tested in the autoimmune encephalitis group. Age and sex-matched cohorts of 12 children with AE (11.2+/-3.5y, IQR 9y; 5M:7F) and 12 typically developing controls (10.6+/-3.2y, IQR 7y; 8M:4F) participated in this study. On average, children with autoimmune encephalitis did not differ from controls in working memory (t(21)= 1.449; p = .162; d = 0.605) but had a significantly lower processing speed (t(21) = 2.463; p = .023; Cohens d = 1.028). The groups did not differ in theta network topology measures but the autoimmune encephalitis group had a significantly lower delta local efficiency across all thresholds tested (d = -1.60 at network threshold 14%). Theta modularity was associated with lower working memory (β = -.781; t(8) = -2.588, p = .032) but this effect did not survive correction for multiple comparisons (p(corr) = .224). No other graph measure was significantly associated with psychometric scores in the autoimmune encephalitis group. MEG was able to capture network alterations in paediatric autoimmune encephalitis patients, specifically in the topological organisation of delta brain activity. This preliminary study demonstrates that MEG is an appropriate tool for assessing children with autoimmune encephalitis; future studies should focus on confirming which functional networks can predict cognitive performance.

The authors have declared no competing interest.

The current study was supported by a European Research Council (ERC) - Consolidator Grant (ERC-CoG) to AW [grant number 682734] and internal grant funding from the Aston Institute of Health and Neurodevelopment to AW and DGK. DGK was funded by a Birmingham Womens and Childrens Hospital Charity Research Fund Grant [BWCHRF572, 37-6-094] to AW SW & EW. CB was funded by a Silver Jubilee PhD studentship from the Encephalitis Society (now Encephalitis International) to AW and SW. SW was supported by a Wellcome Trust Fellowship [216613/Z/19/Z].

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Aston University Ethics Panel of Aston University Ethics reference #18/LO/0990 (#IRAS 233424) gave ethical approval for this work. Aston University Ethics Panel of Aston University reference #HLS21011 gave ethical approval for this work. Aston University was the study sponsor for both healthy and disease cohorts.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The data that support the findings of this study are available from the corresponding author, upon reasonable request.