It was May 26, 2021 when we introduced Dr. Amaia Muñoz Lopetegi. Click here for last year’s post where we learned about her, her study plans and how her project would help patients and families affected by AE.
In the 2021 AEA Community Seed Grant Final Report, Dr. Munoz-Lopetegi explains the outcomes of her project, Subclinical activity in anti-LGI1 encephalitis: diagnostic tests and prognostic implications.
1) Determine whether patients with unrecognized symptoms revealed by our study (e.g., sleep dysfunction, nocturnal faciobrachial dystonic seizures (FBDS) and other seizures) are more likely to have cognitive and psychiatric deficits compared with those without these alterations, and whether these unrecognized symptoms affect cognitive and psychiatric outcomes at 1 year follow-up.
We have included 22 patients to our study and 16 have already reached the 1-year follow- up after 4 visits (inclusion, 3, 6, and 12 months). Each visit consists of 2 days and 1 night admission during which the patient undergoes an extensive panel of neurologic, cognitive, and psychiatric investigations, along with comprehensive sleep assessment, one-night video-polysomnography (V-PSG), and 30-minute electroencephalography (EEG) the next morning.
All patients were included after immunotherapy and symptom improvement and stabilization. However, at visit 1 we found under-recognized nocturnal focal onset epileptic seizures in 8 (36%) of 22 patients and FBDS in 5 (23%). Sleep efficiency was normal only in 3 (14%) patients, while markedly reduced in 15 (68%) (with long awake periods and very fragmented sleep). Muscle activity or movements suggestive of a REM sleep behavior disorder (RBD) were found in 5 (23%). Cognitive tests were impaired in 18 of the 22 patients (82%) at visit 1. Treatment was intensified by local physicians after the findings at visit 1 (especially persisting seizures or FBDS) in half of the patients. Follow up data is subject of future analysis, but preliminary results suggest that PSG findings improved or disappeared in all patients over time. Cognition improved, but not in all patients and mild deficits persisted after one year in some (follow-up to be completed). We hypothesized that poor nocturnal sleep and seizures may relate to poorer cognitive performance and delayed or hindered improvement, so that treating these aspects may improve and accelerate cognition. This will be analyzed when all follow-ups are concluded.
2) Compare the frequency and types of unrecognized symptoms in patients with anti-LGI1 with those with anti-NMDAR encephalitis, and how these symptoms will modify the current treatment management in the post-acute stage of these diseases. We will also provide the spectrum of prolonged or remaining symptoms for each disease and their potential usefulness as biomarkers of subclinical disease activity and cognitive and psychiatric outcomes.
In previous studies we saw that for most patients with anti-NMDAR encephalitis at the post- acute stage of the disease, the remaining symptoms are part of a slow-recovery process.
However, for a substantial number of patients with anti-LGI1 encephalitis the residual deficits at this stage may be caused or favored by a subclinical active disease. Regarding cognitive deficits, persistent epileptic seizures: 1) indicate active disease that may be (actively) producing cognitive impairment as well, 2) may by themselves favor or perpetuate cognitive symptoms, and 3) produce fragmented nocturnal sleep, that may also impair cognitive performance. As seizures do respond well to immunotherapy, they seem to be a useful biomarker to monitor disease activity, the need of treatment continuation, and treatment response. REM sleep behavior disorder was mild or even residual in most patients at visit 1 and improved during the follow up. We need to analyze whether it could be another marker of disease activity.
The impact of this project will be high because it demonstrates that patients with anti-LGI1 encephalitis have subclinical active disease in the post-acute stage, that improves with intensified immunotherapy regimens. The latter indicates that poor performance at this disease stage my be (at least partly) explained by an immune response still causing alterations that impact cognitive or behavioral functions. The fact that this subclinical activity goes under-recognized in clinical grounds, implies that a better follow-up strategy is needed, with studies that are often not included in routine clinical practice, even though they are usually available (such as sleep studies, prolonged EEG assessment). These paraclinical evaluations seem to be useful biomarkers to determine the need for further immunotherapy that may accelerate the recovery or improve the final outcome.
As indicated above, patients with anti-LGI1 encephalitis develop a subclinical active disease that is potentially treatable; therefore, the current study has direct implications for patients for 3 main reasons, 1) it provides clinical and paraclinical biomarkers for disease follow-up, 2) it helps to identify patients that need adjustment of symptomatic medications or continuation of immunotherapy, and 3) it may shorten the process of recovery and improve cognitive and behavioral outcomes.
The AEA allowed free time to extend the evaluation of these patients and analysis of the paraclinical tests, particularly sleep and EEG investigations. Without this support the detailed evaluation of these studies would have not been possible. We are currently in the process of completing all analysis and developing figures for publication, part of the costs of which will also be covered by the AEA seed support. A highly competitive grant proposal has been presented based on the experience gained from the current Seed grant.
Thank you, Dr. Amaia Muñoz Lopetegi for your research and your commitment to improving the lives of patients and families impacted by AE.
Thank you to the entire AE Alliance Community for contributing during the 2020 Research Network Month which assisted in funding this seed grant project.
Thank you for your contributions this year to fund future research!
Together, we are changing the course of AE.